Secnidazole for use in the treatment of trichomoniasis

ABSTRACT

Embodiments are directed to a secnidazole formulations and the use of a secnidazole formulation for the treatment of trichomoniasis in a subject in need thereof.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a divisional application of U.S. non-provisionalapplication Ser. No. 16/403,176, entitled “Secnidazole For Use In TheTreatment Of Bacterial Vaginosis,” filed May 3, 2019, which is adivisional application of U.S. non-provisional application Ser. No.14/846,505, entitled “Secnidazole For Use In The Treatment Of BacterialVaginosis,” filed Sep. 4, 2015, which is now U.S. Pat. No. 10,335,390,issued Jul. 2, 2019, which claims the benefit of priority to U.S.provisional patent application Ser. No. 62/046,731, entitled“Secnidazole for use in the treatment of bacterial vaginosis,” filed onSep. 5, 2014, and U.S. provisional patent application Ser. No.62/101,636, entitled “Secnidazole for use in the treatment of bacterialvaginosis,” filed on Jan. 9, 2015, each of which is hereby incorporatedby reference in its entirety.

BRIEF SUMMARY OF THE INVENTION

Embodiments described herein are directed to a method of treatingbacterial vaginosis in a subject in need thereof comprisingadministering to the subject a therapeutically effective amount ofsecnidazole in a microgranule formulation. In some embodiments, thesecnidazole in a microgranule formulation is administered orally. Insome embodiments, the secnidazole in a microgranule formulationcomprises a plurality of microgranules. In some embodiments, theplurality of microgranules each have a particle size range of about 400micrometers to about 841 micrometers. In some embodiments, themicrogranule formulation further comprises at least one of sugarspheres, povidone, polyethylene glycol 4000, ethyl acrylatemethylacrylate copolymer sold under the trademark Eudragit NE30D, talc,colloidal silicon dioxide or a combination thereof. In some embodiments,the microgranule formulation further comprises at least one of sugarspheres, povidone, polyethylene glycol 4000, ethyl acrylatemethylacrylate copolymer sold under the trademark Eudragit NE30D, talc,or a combination thereof. In some embodiments, the secnidazole in amicrogranule formulation may be mixed, stirred, or otherwise integratedinto a food substance. In some embodiments, the food substance includes,but is not limited to applesauce, yogurt, and pudding.

In some embodiments, the subject is a female. In some embodiments, thesubject is an otherwise healthy female. In some embodiments, the subjectis a pregnant female. In some embodiments, the subject is an otherwisehealthy pregnant female. In some embodiments, the subject is a femalehaving had 3 or fewer bacterial vaginosis infections/episodes in thepast 12 months. In some embodiments, the subject is a female having had4 or more bacterial vaginosis infections/episodes in the past 12 months.In some embodiments, the subject is a female presenting with anoff-white (milky or gray), thin, homogeneous vaginal discharge, an odor,or a combination thereof. In some embodiments, the subject is a femalepresenting with abnormal vaginal discharge, a positive KOH Whiff test,vaginal fluid pH greater than or equal to 4.7, and the presence of “cluecells” greater than 20% of total epithelial cells or any combinationthereof. In some embodiments, the subject is a female with confirmedbacterial vaginosis. In some embodiments, the female with confirmedbacterial vaginosis presents with an off-white (milky or gray), thin,homogeneous vaginal discharge, an odor, or a combination thereof. Insome embodiments, the subject is a female presenting with abnormalvaginal discharge, a positive KOH Whiff test, vaginal fluid pH greaterthan or equal to 4.7, and the presence of “clue cells” greater than 20%of total epithelial cells or any combination thereof. In someembodiments, the female with confirmed bacterial vaginosis presents withfour Amsel criteria parameters and a gram stain slide Nugent score equalto, or higher than four on bacterial analysis of vaginal samples. Insome embodiments, the four Amsel criteria parameters are abnormalvaginal discharge, a positive KOH Whiff test, vaginal fluid pH greaterthan or equal to 4.7, and the presence of clue cells greater than 20% oftotal epithelial cells. In some embodiments, the subject is a femalewith suspected bacterial vaginosis. In some embodiments, the female withsuspected bacterial vaginosis presents with an off-white (milky orgray), thin, homogeneous vaginal discharge, an odor, or a combinationthereof. In some embodiments, the subject is a female presenting withabnormal vaginal discharge, a positive KOH Whiff test, vaginal fluid pHgreater than or equal to 4.7, and the presence of “clue cells” greaterthan 20% of total epithelial cells or any combination thereof. In someembodiments, the female with suspected bacterial vaginosis presents withfour Amsel criteria parameters. In some embodiments, the four Amselcriteria parameters are abnormal vaginal discharge, a positive KOH Whifftest, vaginal fluid pH greater than or equal to 4.7, and the presence ofclue cells greater than 20% of total epithelial cells.

In some embodiments, the therapeutically effective amount of secnidazolein a microgranule formulation is administered as a single dose. In someembodiments, the therapeutically effective amount of secnidazole in amicrogranule formulation administered as a single dose is the only doserequired to be administered to the subject to achieve a post treatmentclinical outcome, resolution of one or more symptoms of bacterialvaginosis, or a combination thereof. In some embodiments, thetherapeutically effective amount of secnidazole in a microgranuleformulation is 2 grams. In some embodiments, the therapeuticallyeffective amount of secnidazole in a microgranule formulation is anamount of secnidazole in a microgranule formulation that exhibits amaximum plasma concentration (C_(max)) of between about 34.5 μg/ml andabout 58.3 μg/ml in the subject. In some embodiments, thetherapeutically effective amount of secnidazole in a microgranuleformulation is an amount of secnidazole in a microgranule formulationthat exhibits a maximum plasma concentration (C_(max)) of between about17.4 μg/ml and about 26.5 μg/ml in the subject. In some embodiments, thetherapeutically effective amount of secnidazole in a microgranuleformulation is an amount of secnidazole that exhibits a time to maximumplasma concentration (T_(max)) of about 3 hours to about 4.05 hours. Insome embodiments, the therapeutically effective amount of secnidazole ina microgranule formulation is an amount of secnidazole that exhibits atime to maximum plasma concentration (T_(max)) of about 2 hours to about6 hours. In some embodiments, the therapeutically effective amount ofsecnidazole in a microgranule formulation is co-administered with anadditional compound selected from ethinyl estradiol (EE2), norethindrone(NET), and a combination thereof.

Some embodiments further comprise determining a post-treatment clinicaloutcome. In some embodiments, a post-treatment clinical outcome isindicative of a clinical outcome responder. Some embodiments furthercomprise determining a post-treatment clinical outcome. In someembodiments, a post-treatment clinical outcome of clinical cure isdefined as a clinical outcome responder. In some embodiments, a clinicaloutcome responder is a subject with normal vaginal discharge, a negativeKOH Whiff test, and clue cells less than 20% of total epithelial cells,post-treatment. In some embodiments, a clinical outcome responder is asubject with a gram stain slide Nugent score of less than four,post-treatment. In some embodiments, a clinical outcome responder is asubject with normal vaginal discharge, a negative KOH Whiff test, cluecells less than 20% of total epithelial cells), and a gram stain slideNugent score of less than four, post-treatment. In some embodiments,administering to the subject a therapeutically effective amount ofsecnidazole in a microgranule formulation results in better thanexpected effectiveness than FDA-approved drugs used in the treatment ofbacterial vaginosis. In some embodiments, administering to the subject atherapeutically effective amount of secnidazole in a microgranuleformulation results in superior effectiveness than FDA-approved drugsused in the treatment of bacterial vaginosis. In some embodiments,administering to the subject a therapeutically effective amount ofsecnidazole in a microgranule formulation results in a higher rate ofclinical cure than FDA-approved drugs used in the treatment of bacterialvaginosis. In some embodiments, administering to the subject atherapeutically effective amount of secnidazole in a microgranuleformulation results in a better than expected safety profile thanFDA-approved drugs used in the treatment of bacterial vaginosis. In someembodiments, administering to the subject a therapeutically effectiveamount of secnidazole in a microgranule formulation results in a morefavorable safety profile than FDA-approved drugs used in the treatmentof bacterial vaginosis. In some embodiments, the therapeuticallyeffective amount of secnidazole in a microgranule formulation is mixedinto a food substance. In some embodiments, the food substance includes,but is not limited to applesauce, yogurt, and pudding.

Some embodiments further comprise administering an additional compoundselected from ethinyl estradiol (EE2), norethindrone (NET), or acombination thereof. In some embodiments, the additional compound isadministered on the same day as the secnidazole microgranuleformulation. In some embodiments, the additional compound isadministered on a different day than the secnidazole microgranuleformulation. In some embodiments, the secnidazole microgranuleformulation does not affect the contraceptive efficacy of the additionalcompound. In some embodiments, the subject has a resolution of one ormore symptoms of bacterial vaginosis within up to about seven days afteradministration. In some embodiments, the subject has an alleviation ofone or more symptoms of bacterial vaginosis within up to about threedays after administration.

Embodiments herein are directed to a microgranule formulation comprisingsecnidazole, or pharmaceutically acceptable salts thereof. In someembodiments, the microgranule formulation comprises a therapeuticallyeffective amount of secnidazole, or pharmaceutically acceptable saltsthereof. In some embodiments, the microgranule formulation is a delayedrelease formulation. In some embodiments, the delayed releaseformulation, when administered to a subject provides a secnidazoleconcentration profile characterized by a change in secnidazoleconcentration as function of time that is less than that of an immediaterelease secnidazole microgranule formulation. In some embodiments, thedelayed release formulation, when administered to a subject provides asecnidazole concentration profile characterized by a time to maximumplasma concentration (T_(max)) that is greater than that of an immediaterelease secnidazole microgranule formulation. In some embodiments, thedelayed release formulation, when administered to a subject provides asecnidazole concentration profile characterized by a maximum plasmaconcentration (C_(max)) that is greater than that of an immediaterelease secnidazole microgranule formulation. In some embodiments, thedelayed release formulation, when administered to a subject provides asecnidazole concentration profile characterized by a AUC that is greaterthan that of an immediate release secnidazole microgranule formulation.In some embodiments, the microgranule formulation comprises about 1 g toabout 2 g of secnidazole or pharmaceutically acceptable salts thereof.In some embodiments, the microgranule formulation comprises about 2 g ofsecnidazole or pharmaceutically acceptable salts thereof. In someembodiments, the microgranule formulation is suitable for oraladministration. Some embodiments further comprise sugar spheres,povidone, polyethylene glycol 4000, ethyl acrylate methylacrylatecopolymer sold under the trademark Eudragit NE30D, talc, colloidalsilicon dioxide or any combination thereof. In some embodiments, themicrogranule formulation further comprises at least one of sugarspheres, povidone, polyethylene glycol 4000, ethyl acrylatemethylacrylate copolymer sold under the trademark Eudragit NE30D, talc,colloidal silicon dioxide or a combination thereof. Some embodimentsfurther comprise polyethylene glycol 4000 and ethyl acrylatemethylacrylate copolymer sold under the trademark Eudragit NE30D. Insome embodiments, the microgranule formulation comprises a plurality ofmicrogranules. In some embodiments, the plurality of microgranules eachhave a particle size range of about 400 micrometers to about 841micrometers.

BRIEF DESCRIPTION OF THE FIGURES

FIG. 1 illustrates the mean (±SD) SYM-1219 plasma concentration (μg/mL)for the 1 g dose (circle markers) and the 2 g dose (triangle markers)over time.

FIG. 2 illustrates the mean (±SD) EE2 plasma concentrations (pg/mL) forGroup B1 over time where (1) EE2 was administered alone (circle markers)on Day 1 of Period 1; and (2) EE2 was administered in conjunction with 2gram microgranule formulation SYM-1219 on Day 1 of Period 2 (trianglemarkers).

FIG. 3 illustrates the mean (±SD) EE2 plasma concentrations (pg/mL) forGroup B2 over time where (1) EE2 was administered alone (circle markers)on Day 1 of Period 1; and (2) 2 gram microgranule formulation SYM-1219was administered on Day 1 of Period 2 and EE2 was administered on Day 2of Period 2 (triangle markers).

FIG. 4 illustrates the mean (±SD) NET plasma levels (ng/mL) for Group B1over time where (1) NET alone was administered on Day 1 of Period 1(circle markers), and (2) NET followed by 2 gram microgranuleformulation of SYM-1219 was administered on Day 1 of Period 2 (trianglemarkers).

FIG. 5 illustrates the mean (±SD) NET plasma levels (ng/mL) for Group B2over time where (1) NET alone was administered on Day 1 of Period 1(circle markers), and (2) 2 gram microgranule formulation of SYM-1219was administered on Day 1 of Period 2 and NET was administered on Day 2of Period 2 (triangle markers).

DETAILED DESCRIPTION

Before the present formulations and methods are described, it is to beunderstood that this invention is not limited to the particularprocesses, compounds, or methodologies described, as these may vary. Itis also to be understood that the terminology used in the description isfor the purpose of describing the particular versions or embodimentsonly, and is not intended to limit the scope of the present invention.Unless defined otherwise, all technical and scientific terms used hereinhave the same meanings as commonly understood by one of ordinary skillin the art. Although any methods and materials similar or equivalent tothose described herein can be used in the practice or testing ofembodiments of the present invention, the preferred methods, devices,and materials are now described. All publications mentioned herein areincorporated by reference in their entirety.

Secnidazole [1-(2-hydroxypropyl)-2-methyl-5-nitromidazole] is a5-nitroimidazole derivative compound. Embodiments described in thisdocument are directed to secnidazole (and pharmaceutically acceptablesalts thereof) formulations (such as SYM-1219) and the use of asecnidazole formulation for the treatment of bacterial vaginosis.

In some embodiments, the secnidazole formulation comprises a secnidazolemicrogranule formulation. In some embodiments, the secnidazolemicrogranule formulation is a delayed release formulation. In someembodiments, a delayed release formulation, when administered to asubject that provides a secnidazole concentration profile characterizedby a change in secnidazole concentration as function of time that isless than that of an immediate release secnidazole microgranuleformulation. In some embodiments, the secnidazole microgranuleformulation comprises about 1 g to about 2 g of secnidazole orpharmaceutically acceptable salts thereof. In some embodiments, thesecnidazole microgranule formulation comprises about 2 g of secnidazoleor pharmaceutically acceptable salts thereof. In some embodiments, thesecnidazole microgranule formulation may be suitable for oraladministration. In some embodiments, the microgranule formulation mayfurther comprise one or more of the following ingredients selected fromsugar spheres, povidone, polyethylene glycol 4000, Eudragit NE30D, talc,and colloidal silicon dioxide. In some embodiments, the microgranuleformulation may further comprise one or more of the followingingredients selected from sugar spheres, povidone, polyethylene glycol4000, ethyl acrylate methylacrylate copolymer sold under the trademarkEudragit NE30D, and talc. In some embodiments, the secnidazolemicrogranule formulation comprises a plurality of microgranules. In someembodiments, the plurality of microgranules are white to off-white incolor. In some embodiments, the plurality of microgranules each have aparticle size range of about 400 micrometers to about 841 micrometers.In some embodiments, the microgranules are packaged as unit doses. Insome embodiments, the microgranules are packaged as single unit doses.In some embodiments, the microgranules are packaged in such a way as toprovide a barrier to oxygen and moisture. In some embodiments, themicrogranules are packaged in a foil pouch or sachet. In someembodiments, the foil pouch or sachet is made of a polyester-facedlaminated or polyethylene-metallocene-lined aluminum foil pouchingmaterial that provides a barrier to oxygen and moisture. In someembodiments, the pouch or sachet is made from a material such as, butnot limited to, Fasson® Rapid-Roll® White Cosmetic Web 350 HB.

In some embodiments, a method of making the secnidazole microgranuleformulation comprises coating sugar spheres. In some embodiments, thecoating is a process, such as a four-step process. In some embodiments,the process comprises layering the secnidazole on the spheres, sealcoating with polyethylene glycol 4000, coating with ethyl acrylatemethylacrylate copolymer sold under the trademark Eudragit NE30D, andcuring. In some embodiments, coating with Eudragit provides a delayedrelease formulation. In some embodiments, a method of making thesecnidazole microgranule formulation comprises blending with talc. Insome embodiments, blending with talc increases the flowability of thesecnidazole microgranule formulation.

In some embodiments, a method of making the secnidazole microgranuleformulation comprises coating sugar spheres. In some embodiments, thecoating is a process, such as a three-step process. In some embodiments,the process comprises layering the secnidazole on the spheres, coatingwith ethyl acrylate methylacrylate copolymer sold under the trademarkEudragit NE30D, and curing. In some embodiments, coating with Eudragitprovides a delayed release formulation. In some embodiments, a method ofmaking the secnidazole microgranule formulation comprises blending withtalc. In some embodiments, blending with talc increases the flowabilityof the secnidazole microgranule formulation.

In some embodiments, a method of treating bacterial vaginosis in asubject in need thereof comprises administering to the subject atherapeutically effective amount of secnidazole or pharmaceuticallyacceptable salts thereof. In some embodiments, a method of treatingbacterial vaginosis in a subject in need thereof comprises administeringto the subject a therapeutically effective amount of secnidazole orpharmaceutically acceptable salts thereof in a microgranule formulation.In some embodiments, the secnidazole microgranule formulation may besuitable for oral administration. In some embodiments, the secnidazolemicrogranule formulation comprises a plurality of microgranules. In someembodiments, the plurality of microgranules are white to off-white incolor. In some embodiments, the plurality of microgranules each have aparticle size range of about 400 micrometers to about 841 micronsmicrometers. In some embodiments, the secnidazole microgranuleformulation may be mixed, stirred, or otherwise integrated into a foodsubstance. In some embodiments, the food substance may be a semisolid orsoft food. In some embodiments, the food substance may include, but isnot limited to applesauce, pudding, yogurt or the like. In someembodiments, integration of the secnidazole microgranule formulationinto a food substance has a taste masking function.

In some embodiments, the subject is a human. In yet other embodiments,the subject is a human female. In some embodiments, the human female isof an age ranging from a postmenarachal adolescent to a premenopausalwoman. In some embodiments, the subject is a pregnant human female.

In some embodiments, the subject is a female. In some embodiments, thesubject is an otherwise healthy female. In some embodiments, the subjectis a pregnant female. In some embodiments, the subject is an otherwisehealthy pregnant female. In some embodiments, the subject is a femalehaving had 3 or fewer bacterial vaginosis infections in the past 12months. In some embodiments, the subject is a female having had 4 ormore bacterial vaginosis infections in the past twelve months. In someembodiments, the subject is a female with recurring bacterial vaginosis.In some embodiments, a subject with recurring bacterial vaginosis is asubject with 4 or more bacterial vaginosis infections within atwelve-month period. In some embodiments, the subject is a female withfrequent bacterial vaginosis infections. In some embodiments, a femalewith frequent bacterial vaginosis infections is a female with 4 or morebacterial vaginosis infections within a twelve-month period. In someembodiments, the subject is a female presenting with an off-white (milkyor gray), thin, homogeneous vaginal discharge, vaginal pH greater thanor equal to 4.7, presence of clue cells of greater than or equal to 20%of the total epithelial cells on microscopic examination of a vaginalsaline wet mount, a positive 10% KOH Whiff test or a combinationthereof. In some embodiments, the subject is a female presenting with anoff-white (milky or gray), thin, homogeneous vaginal discharge, vaginalpH greater than or equal to 4.7, the presence of clue cells of greaterthan or equal to 20% of the total epithelial cells on microscopicexamination of a vaginal saline wet mount, and a positive 10% KOH Whifftest. In some embodiments, the subject is a female with confirmedbacterial vaginosis. In some embodiments, bacterial vaginosis isconfirmed by the presence of four (4) Amsel criteria parameters selectedfrom an off-white (milky or gray), thin, homogeneous vaginal discharge,vaginal pH greater than or equal to 4.7, the presence of clue cells ofgreater than or equal to 20% of the total epithelial cells onmicroscopic examination of a vaginal saline wet mount, a positive 10%KOH Whiff test and a gram stain slide Nugent score equal to, or higherthan four (4) on bacterial analysis of vaginal samples. In someembodiments, the subject is a female with suspected bacterial vaginosis.In some embodiments, suspected bacterial vaginosis is indicated by thepresence of four (4) Amsel criteria parameters selected from anoff-white (milky or gray), thin, homogeneous vaginal discharge, vaginalpH greater than or equal to 4.7, the presence of clue cells of greaterthan or equal to 20% of the total epithelial cells on microscopicexamination of a vaginal saline wet mount, and a positive 10% KOH Whifftest. In some embodiments, the subject is a female presenting with anoff-white (milky or gray), thin, homogeneous vaginal discharge, odor, ora combination thereof.

In some embodiments, a method of treating bacterial vaginosis in asubject comprises administering to the subject a single dose of atherapeutically effective amount of secnidazole in a microgranuleformulation, wherein the secnidazole comprises about 1 g to about 2 g ofthe microgranule formulation. In some embodiments, the secnidazolemicrogranule formulation is co-administered with an additional compoundselected from ethinyl estradiol (EE2), norethindrone (NET), or acombination thereof. In some embodiments, the secnidazole microgranuleformulation is mixed into a semisolid or soft food substance, such asbut not limited to applesauce yogurt and pudding. In some embodiments,the amount of the food substance is about 4-6 ounces.

In some embodiments, a method of treating bacterial vaginosis in asubject comprises administering to the subject a single dose of asecnidazole microgranule formulation that exhibits a maximum plasmaconcentration (C_(max)) of between about 34.5 μg/ml and about 58.3μg/ml. In some embodiments, a method of treating bacterial vaginosis ina subject comprises administering to the subject a single dose of asecnidazole microgranule formulation that exhibits a maximum plasmaconcentration (C_(max)) of between about 17.4 μg/ml and about 26.5μg/ml.

In some embodiments, a method of treating bacterial vaginosis in asubject comprises administering to the subject a single dose of asecnidazole microgranule formulation that exhibits a time to maximumplasma concentration (T_(max)) of about 3 hours to about 4.05 hours. Insome embodiments, a method of treating bacterial vaginosis in a subjectcomprises administering to the subject a single dose of a secnidazolemicrogranule formulation that exhibits a time to maximum plasmaconcentration (T_(max)) of about 2 hours to about 6 hours.

In some embodiments, a method of treating bacterial vaginosis in asubject comprises co-administering to the subject a single dose of atherapeutically effective amount of secnidazole in a microgranuleformulation and an additional compound selected from ethinyl estradiol(EE2), norethindrone (NET), or a combination thereof, wherein thesecnidazole comprises about 1 g to about 2 g of the microgranuleformulation. In some embodiments, the additional compound isco-administered on the same day as the secnidazole microgranuleformulation. In some embodiments, the additional compound isadministered on a different day than the secnidazole microgranuleformulation. In some embodiments, the secnidazole microgranuleformulation does not affect the contraceptive efficacy of the additionalcompound.

In some embodiments, a method of treating bacterial vaginosis in asubject further comprises determining a post treatment clinical outcome.In some embodiments, a post treatment clinical outcome is indicative ofa clinical outcome responder. Some embodiments further comprisedetermining a post-treatment clinical outcome. In some embodiments, apost-treatment clinical outcome of clinical cure is defined as aclinical outcome responder. In some embodiments, a clinical outcomeresponder is a subject with normal vaginal discharge, a negative KOHWhiff test, and clue cells less than or equal to 20% of the totalepithelial cells on microscopic examination of a vaginal saline wetmount after treatment with a microgranule formulation comprising about 1to about 2 grams of secnidazole. In some embodiments, a clinical outcomeresponder has a gram stain slide Nugent score of less than four (4)after treatment with a single dose of secnidazole. In yet otherembodiments, a clinical outcome responder is a subject with normalvaginal discharge, a negative KOH Whiff test, clue cells less than 20%of total epithelial cells, and a gram stain slide Nugent score of lessthan four (4) after treatment with a single dose of secnidazole. In someembodiments, a clinical outcome responder has a gram stain slide Nugentscore of less than four (4) after treatment with a 2 gram single dose ofsecnidazole. In yet other embodiments, a clinical outcome responder is asubject with normal vaginal discharge, a negative KOH Whiff test, cluecells less than 20% of total epithelial cells, and a gram stain slideNugent score of less than four (4) after treatment with a 2 gram singledose of secnidazole. In some embodiments, a post-treatment clinicaloutcome is observable after about 24 hours after administration. In someembodiments, a post-treatment clinical outcome is observable after about48 hours after administration. In some embodiments, a post-treatmentclinical outcome is observable after about 72 hours afteradministration. In some embodiments, a post-treatment clinical outcomeis observable after about 96 hours after administration. In someembodiments, a post-treatment clinical outcome is observable after about120 hours after administration. In some embodiments, a post-treatmentclinical outcome is observable after about 168 hours afteradministration. In some embodiments, a post-treatment clinical outcomeis observable after about 7 to about 10 days after administration. Insome embodiments, a post-treatment clinical outcome is observable afterabout 11 to about 20 days after administration. In some embodiments, apost-treatment clinical outcome is observable after about 21 to about 30days after administration.

In some embodiments, a method of treating bacterial vaginosis furthercomprises an alleviation of one or more symptoms of bacterial vaginosiswithin up to about three days after administration to the subject. Insome embodiments, a method of treating bacterial vaginosis furthercomprises an alleviation of one or more symptoms of bacterial vaginosiswithin up to about three days after administration to the subject. Insome embodiments, the one or more symptoms include, but are not limitedto, abnormal vaginal odor, abnormal vaginal discharge or a combinationthereof. In some embodiments, alleviation refers to a lessening of theseverity of one or more symptoms. In some embodiments, alleviation ofone or more symptoms of bacterial vaginosis occurs within about 24 hoursafter administration. In some embodiments, alleviation of one or moresymptoms of bacterial vaginosis occurs within about 48 hours afteradministration. In some embodiments, alleviation of one or more symptomsof bacterial vaginosis occurs within about 72 hours after administrationto the subject. In some embodiments, alleviation of one or more symptomsof bacterial vaginosis occurs within about 96 hours after administrationto the subject. In some embodiments, alleviation of one or more symptomsof bacterial vaginosis occurs within about 120 hours afteradministration to the subject. In some embodiments, alleviation of oneor more symptoms of bacterial vaginosis occurs within about 168 hoursafter administration to the subject. In some embodiments, alleviation ofone or more symptoms of bacterial vaginosis occurs within about 7 toabout 10 days after administration to the subject. In some embodiments,alleviation of one or more symptoms of bacterial vaginosis occurs withinabout 11 to about 20 days after administration to the subject. In someembodiments, alleviation of one or more symptoms of bacterial vaginosisoccurs within about 21 to about 30 days after administration to thesubject.

In some embodiments, a method of treating bacterial vaginosis furthercomprises a resolution of one or more symptoms of bacterial vaginosiswithin up to about seven days after administration to the subject. Insome embodiments, a method of treating bacterial vaginosis furthercomprises a resolution of one or more symptoms of bacterial vaginosiswithin up to about seven days after administration to the subject. Insome embodiments, the one or more symptoms include, but are not limitedto, abnormal vaginal odor, abnormal vaginal discharge or a combinationthereof. In some embodiments, resolution of one or more symptoms ofbacterial vaginosis occurs within about 24 hours after administration tothe subject. In some embodiments, resolution of one or more symptoms ofbacterial vaginosis occurs within about 48 hours after administration.In some embodiments, resolution of one or more symptoms of bacterialvaginosis occurs within about 72 hours after administration to thesubject. In some embodiments, resolution of one or more symptoms ofbacterial vaginosis occurs within about 96 hours after administration tothe subject. In some embodiments, resolution of one or more symptoms ofbacterial vaginosis occurs within about 120 hours after administrationto the subject. In some embodiments, resolution of one or more symptomsof bacterial vaginosis occurs within about 168 hours afteradministration to the subject. In some embodiments, resolution of one ormore symptoms of bacterial vaginosis occurs within about 7 to about 10days after administration to the subject. In some embodiments,resolution of one or more symptoms of bacterial vaginosis occurs withinabout 11 to about 20 days after administration to the subject. In someembodiments, resolution of one or more symptoms of bacterial vaginosisoccurs within about 21 to about 30 days after administration to thesubject.

In some embodiments, treatment of bacterial vaginosis with a single, 2gram dose of secnidazole in a microgranule formulation results in betterthan expected efficacy compared with FDA approved drugs used in thetreatment of bacterial vaginosis. In some embodiments, treatment ofbacterial vaginosis with a single, 2 gram dose of secnidazole in amicrogranule formulation results in superior effectiveness compared withother FDA-approved drugs used in the treatment of bacterial vaginosis.In some embodiments, treatment of bacterial vaginosis with a single, 2gram dose of secnidazole in a microgranule formulation results in ahigher rate of clinical cure than FDA-approved drugs used in thetreatment of bacterial vaginosis. In some embodiments, a clinicaloutcome responder is a subject with normal vaginal discharge, a negativeKOH Whiff test, and clue cells less than or equal to 20% of the totalepithelial cells on microscopic examination of a vaginal saline wetmount after treatment In some embodiments, a single dose of 2 grams ofsecnidazole results in a better than expected efficacy compared with FDAapproved drugs currently used in the treatment of bacterial vaginosis.In some embodiments, treatment of bacterial vaginosis with a single, 2gram dose of secnidazole results in superior efficacy compared with FDAapproved drugs used in the treatment of bacterial vaginosis. In someembodiments, a single dose of 2 grams of secnidazole results in superiorefficacy compared with FDA drugs used in the treatment of bacterialvaginosis requiring multiple doses during treatment. For example,Secnidazole has been shown to have a higher rate of clinical cure after21-30 days of treatment (67.7% clinical cure after a single, 2 g oraldose) compared with other FDA approved drugs for the treatment ofbacterial vaginosis (Nuvessa—37% after vaginal single application;Tindamax—35.6% after 3 day oral regimen and 51.3% after 5 day oralregimen; Clindesse—41.0-53.45 clinical cure after vaginal singleapplication; Flagyl ER—61.1—62.2% clinical cure after 7 day oralregimen; and Metrogel-Vaginal—53.0% after 5 day vaginal regimen (allclinical cure rates are 21-30 days after treatment)).

In some embodiments, treatment of bacterial vaginosis with a single, 2gram dose of secnidazole results in a better than expected safetyprofile compared with FDA approved drugs used in the treatment ofbacterial vaginosis. In some embodiments, a single dose of 2 grams ofsecnidazole results in a better than expected safety profile comparedwith FDA approved drugs used in the treatment of bacterial vaginosisrequiring multiple doses during treatment. In some embodiments,treatment of bacterial vaginosis with a single, 2 gram dose ofsecnidazole results in a superior safety profile compared with FDAapproved drugs used in the treatment of bacterial vaginosis. In someembodiments, a single dose of 2 grams of secnidazole results in asuperior safety profile compared with FDA approved drugs used in thetreatment of bacterial vaginosis requiring multiple doses duringtreatment. In some embodiments, treatment of bacterial vaginosis with asingle, 2 gram dose of secnidazole in a microgranule formulation resultsin a better than expected safety profile compared with FDA approveddrugs used in the treatment of bacterial vaginosis. In some embodiments,a single dose of 2 grams of secnidazole in a microgranule formulationresults in a better than expected safety profile compared with FDAapproved drugs used in the treatment of bacterial vaginosis requiringmultiple doses during treatment. In some embodiments, treatment ofbacterial vaginosis with a single, 2 gram dose of secnidazole in amicrogranule formulation results in a superior safety profile comparedwith FDA approved drugs used in the treatment of bacterial vaginosis. Insome embodiments, a single dose of 2 grams of secnidazole in amicrogranule formulation results in a superior safety profile comparedwith FDA approved drugs used in the treatment of bacterial vaginosisrequiring multiple doses during treatment. In some embodiments, multipledoses may be given at pre-determined intervals such as but not limitedto once a week, bi-weekly, monthly, bimonthly for the duration oftreatment. In some embodiment, the duration of treatment may be at leastone week. In some embodiment, the duration of treatment may be at leastone month. In some embodiments, the duration of treatment is about sixmonths. For example, as can be seen in Table 1, secnidazole has superiorsafety profile compared with other FDA approved drugs for the treatmentof bacterial vaginosis.

TABLE 1 Comparison of key adverse events Secnidazole Metrogel- 2 gramsFlagyl ER Clindesse Vaginal Adverse Event (n = 72) (N = 267) (n = 368)(n = 505) Headache 1% 18%  3% 5% Nausea 1% 10%  1% 4% Abdominal pain 0%4% 1% Not reported Diarrhea 0% 4% 1% 1% Metallic/Unusual 1% 9% Not 2%Taste reported Fungal Infection 3% Not 14%  10%  reported Vulva/Vaginal1% Not 3% 9% Irritation reported

In some embodiments, treatment of bacterial vaginosis with a single, 2gram dose of secnidazole results in better than expected efficacycompared with FDA approved drugs used in the treatment of bacterialvaginosis in subjects with frequent bacterial vaginosis infections. Insome embodiments, a single dose of 2 grams of secnidazole results in abetter than expected efficacy compared with FDA approved drugs used inthe treatment of bacterial vaginosis requiring multiple doses duringtreatment in subjects with frequent bacterial vaginosis infections. Insome embodiments, treatment of bacterial vaginosis with a single, 2 gramdose of secnidazole results in superior efficacy compared with FDAapproved drugs used in the treatment of bacterial vaginosis in subjectswith frequent bacterial vaginosis infections. In some embodiments, asingle dose of 2 grams of secnidazole results in superior efficacycompared with FDA approved drugs used in the treatment of bacterialvaginosis requiring multiple doses during treatment in subjects withfrequent bacterial vaginosis infections. In some embodiments, subjectswith frequent bacterial vaginosis infections are subjects with 4 or morebacterial vaginosis infections within a twelve month period.

In some embodiments, treatment of bacterial vaginosis with a single, 2gram dose of secnidazole results in better than expected safety profilecompared with FDA approved drugs used in the treatment of bacterialvaginosis with frequent bacterial vaginosis infections. In someembodiments, a single dose of 2 grams of secnidazole results in a betterthan expected safety profile compared with FDA approved drugs used inthe treatment of bacterial vaginosis requiring multiple doses duringtreatment in subjects with frequent bacterial vaginosis infections. Insome embodiments, treatment of bacterial vaginosis with a single, 2 gramdose of secnidazole results in a superior safety profile compared withFDA approved drugs used in the treatment of bacterial vaginosis insubjects with frequent bacterial vaginosis infections. In someembodiments, a single dose of 2 grams of secnidazole results in asuperior safety profile compared with FDA approved drugs used in thetreatment of bacterial vaginosis requiring multiple doses duringtreatment in subjects with frequent bacterial vaginosis infections. Insome embodiments, subjects with frequent bacterial vaginosis infectionsare those with 4 or more bacterial vaginosis infections within a twelvemonth period.

In some embodiments, a method of treating bacterial vaginosis in asubject in need thereof further comprises administering to at least oneof the subjects' sexual partners, a therapeutically effective amount ofsecnidazole or pharmaceutically acceptable salts thereof. In someembodiments, a method of treating bacterial vaginosis in a subject inneed thereof further comprises administering to at least one of thesubjects' sexual partners, a therapeutically effective amount ofsecnidazole or pharmaceutically acceptable salts thereof in amicrogranule formulation. In some embodiments, the secnidazolemicrogranule formulation may be suitable for oral administration. Insome embodiments, the secnidazole microgranule formulation comprises aplurality of microgranules. In some embodiments, the plurality ofmicrogranules are white to off-white in color. In some embodiments, theplurality of microgranules each have a particle size range of about 400micrometers to about 841 micrometers. In some embodiments, thesecnidazole microgranule formulation may be mixed, stirred, or otherwiseintegrated into a food substance. In some embodiments, the foodsubstance may be a semisolid or soft food. In some embodiments, the foodsubstance may include, but is not limited to applesauce, pudding, yogurtor the like. In some embodiments, integration of the secnidazolemicrogranule formulation into a food substance has a taste maskingfunction. In some embodiments, the at least one sexual partner of thesubject may be a male or a female. In some embodiments, a single dose ofa therapeutically effective amount of secnidazole or pharmaceuticallyacceptable salts thereof may be administered. In some embodiments, asingle dose of a therapeutically effective amount of secnidazole orpharmaceutically acceptable salts thereof in a microgranule formulationmay be administered. In some embodiments, multiple doses may be given atpre-determined intervals such as but not limited to once a week,bi-weekly, monthly, bimonthly for the duration of treatment. In someembodiment, the duration of treatment may be at least one week. In someembodiment, the duration of treatment may be at least one month. In someembodiments, the duration of treatment is about six months.

Some embodiments are directed to a method of reducing the incidenceand/or risk of a preterm birth. Bacterial vaginosis infections mayincrease the risk of a preterm birth in a subject. In some embodiments,a method of reducing the incidence and/or risk of a preterm birth in asubject comprises administering to the subject a therapeuticallyeffective amount of secnidazole or pharmaceutically acceptable saltsthereof. In some embodiments, a method of reducing the incidence and/orrisk of a preterm birth in a subject comprises administering to thesubject a therapeutically effective amount of secnidazole orpharmaceutically acceptable salts thereof in a microgranule formulation.In some embodiments, the secnidazole microgranule formulation may besuitable for oral administration. In some embodiments, the secnidazolemicrogranule formulation comprises a plurality of microgranules. In someembodiments, the plurality of microgranules are white to off-white incolor. In some embodiments, the plurality of microgranules each have aparticle size range of about 400 micrometers to about 841 micrometers.In some embodiments, the secnidazole microgranule formulation may bemixed, stirred, or otherwise integrated into a food substance. In someembodiments, the food substance may be a semisolid or soft food. In someembodiments, the food substance may include, but is not limited toapplesauce, pudding, yogurt or the like. In some embodiments,integration of the secnidazole microgranule formulation into a foodsubstance has a taste masking function. In some embodiments, the subjectis a human. In yet other embodiments, the subject is a pregnant humanfemale.

In some embodiments, the subject is a female. In some embodiments, thesubject is an otherwise healthy female. In some embodiments, the subjectis a pregnant female. In some embodiments, the subject is an otherwisehealthy pregnant female. In some embodiments, the subject is a femalehaving had 3 or fewer bacterial vaginosis infections in the past 12months. In some embodiments, the subject is a female having had 4 ormore bacterial vaginosis infections in the past twelve months. In someembodiments, the subject is a female with recurring bacterial vaginosis.In some embodiments, a subject with recurring bacterial vaginosis is asubject with 4 or more bacterial vaginosis infections within atwelve-month period. In some embodiments, the subject is a female withfrequent bacterial vaginosis infections. In some embodiments, a femalewith frequent bacterial vaginosis infections is a female with 4 or morebacterial vaginosis infections within a twelve-month period. In someembodiments, the subject is a female presenting with an off-white (milkyor gray), thin, homogeneous vaginal discharge, vaginal pH greater thanor equal to 4.7, presence of clue cells of greater than or equal to 20%of the total epithelial cells on microscopic examination of a vaginalsaline wet mount, a positive 10% KOH Whiff test or a combinationthereof. In some embodiments, the subject is a female presenting with anoff-white (milky or gray), thin, homogeneous vaginal discharge, vaginalpH greater than or equal to 4.7, the presence of clue cells of greaterthan or equal to 20% of the total epithelial cells on microscopicexamination of a vaginal saline wet mount, and a positive 10% KOH Whifftest. In some embodiments, the subject is a female with confirmedbacterial vaginosis. In some embodiments, bacterial vaginosis isconfirmed by the presence of four (4) Amsel criteria parameters selectedfrom an off-white (milky or gray), thin, homogeneous vaginal discharge,vaginal pH greater than or equal to 4.7, the presence of clue cells ofgreater than or equal to 20% of the total epithelial cells onmicroscopic examination of a vaginal saline wet mount, a positive 10%KOH Whiff test and a gram stain slide Nugent score equal to, or higherthan four (4) on bacterial analysis of vaginal samples. In someembodiments, the subject is a female with suspected bacterial vaginosis.In some embodiments, suspected bacterial vaginosis is indicated by thepresence of four (4) Amsel criteria parameters selected from anoff-white (milky or gray), thin, homogeneous vaginal discharge, vaginalpH greater than or equal to 4.7, the presence of clue cells of greaterthan or equal to 20% of the total epithelial cells on microscopicexamination of a vaginal saline wet mount, and a positive 10% KOH Whifftest. In some embodiments, the subject is a female presenting with anoff-white (milky or gray), thin, homogeneous vaginal discharge, odor, ora combination thereof.

In some embodiments, a method of reducing the incidence and/or risk of apreterm birth in a subject comprises administering to the subject asingle dose of a therapeutically effective amount of secnidazole in amicrogranule formulation, wherein the secnidazole comprises about 1 g toabout 2 g of the microgranule formulation. In some embodiments, thesecnidazole microgranule formulation is co-administered with anadditional compound selected from ethinyl estradiol (EE2), norethindrone(NET), or a combination thereof. In some embodiments, the secnidazolemicrogranule formulation is mixed into a semisolid or soft foodsubstance, such as but not limited to applesauce yogurt and pudding. Insome embodiments, the amount of the food substance is about 4-6 ounces.

In some embodiments, a method of reducing the incidence and/or risk of apreterm birth in a subject comprises administering to the subject asingle dose of a secnidazole microgranule formulation that exhibits amaximum plasma concentration (C_(max)) of between about 34.5 μg/ml andabout 58.3 μg/ml. In some embodiments, a method of treating bacterialvaginosis in a subject comprises administering to the subject a singledose of a secnidazole microgranule formulation that exhibits a maximumplasma concentration (C_(max)) of between about 17.4 μg/ml and about26.5 μg/ml.

In some embodiments, a method of reducing the incidence and/or risk of apreterm birth in a subject comprises administering to the subject asingle dose of a secnidazole microgranule formulation that exhibits atime to maximum plasma concentration (T_(max)) of about 3 hours to about4.05 hours. In some embodiments, a method of treating bacterialvaginosis in a subject comprises administering to the subject a singledose of a secnidazole microgranule formulation that exhibits a time tomaximum plasma concentration (T_(max)) of about 2 hours to about 6hours.

In some embodiments, a method of reducing the incidence and/or risk of apreterm birth in a subject further comprises a term birth. In someembodiments, a method of reducing the incidence and/or risk of a pretermbirth in a subject further comprises determining a post treatmentclinical outcome. In some embodiments, a post treatment clinical outcomeis indicative of a clinical outcome responder. Some embodiments furthercomprise determining a post-treatment clinical outcome. In someembodiments, a post-treatment clinical outcome of clinical cure isdefined as a clinical outcome responder. In some embodiments, a clinicaloutcome responder is a subject with normal vaginal discharge, a negativeKOH Whiff test, and clue cells less than or equal to 20% of the totalepithelial cells on microscopic examination of a vaginal saline wetmount after treatment with a microgranule formulation comprising about 1to about 2 grams of secnidazole. In some embodiments, a clinical outcomeresponder has a gram stain slide Nugent score of less than four (4)after treatment with a single dose of secnidazole. In yet otherembodiments, a clinical outcome responder is a subject with normalvaginal discharge, a negative KOH Whiff test, clue cells less than 20%of total epithelial cells, and a gram stain slide Nugent score of lessthan four (4) after treatment with a single dose of secnidazole. In someembodiments, a clinical outcome responder has a gram stain slide Nugentscore of less than four (4) after treatment with a 2 gram single dose ofsecnidazole. In yet other embodiments, a clinical outcome responder is asubject with normal vaginal discharge, a negative KOH Whiff test, cluecells less than 20% of total epithelial cells, and a gram stain slideNugent score of less than four (4) after treatment with a 2 gram singledose of secnidazole. In some embodiments, a post-treatment clinicaloutcome is observable after about 24 hours after administration. In someembodiments, a post-treatment clinical outcome is observable after about48 hours after administration. In some embodiments, a post-treatmentclinical outcome is observable after about 72 hours afteradministration. In some embodiments, a post-treatment clinical outcomeis observable after about 96 hours after administration. In someembodiments, a post-treatment clinical outcome is observable after about120 hours after administration. In some embodiments, a post-treatmentclinical outcome is observable after about 168 hours afteradministration. In some embodiments, a post-treatment clinical outcomeis observable after about 7 to about 10 days after administration. Insome embodiments, a post-treatment clinical outcome is observable afterabout 11 to about 20 days after administration. In some embodiments, apost-treatment clinical outcome is observable after about 21 to about 30days after administration.

In some embodiments, a method of reducing the incidence and/or risk of apreterm birth in a subject further comprises an alleviation of one ormore symptoms of bacterial vaginosis within up to about three days afteradministration to the subject. In some embodiments, a method of treatingbacterial vaginosis further comprises an alleviation of one or moresymptoms of bacterial vaginosis within up to about three days afteradministration to the subject. In some embodiments, the one or moresymptoms include, but are not limited to, abnormal vaginal odor,abnormal vaginal discharge or a combination thereof. In someembodiments, alleviation refers to a lessening of the severity of one ormore symptoms. In some embodiments, alleviation of one or more symptomsof bacterial vaginosis occurs within about 24 hours afteradministration. In some embodiments, alleviation of one or more symptomsof bacterial vaginosis occurs within about 48 hours afteradministration. In some embodiments, alleviation of one or more symptomsof bacterial vaginosis occurs within about 72 hours after administrationto the subject. In some embodiments, alleviation of one or more symptomsof bacterial vaginosis occurs within about 96 hours after administrationto the subject. In some embodiments, alleviation of one or more symptomsof bacterial vaginosis occurs within about 120 hours afteradministration to the subject. In some embodiments, alleviation of oneor more symptoms of bacterial vaginosis occurs within about 168 hoursafter administration to the subject. In some embodiments, alleviation ofone or more symptoms of bacterial vaginosis occurs within about 7 toabout 10 days after administration to the subject. In some embodiments,alleviation of one or more symptoms of bacterial vaginosis occurs withinabout 11 to about 20 days after administration to the subject. In someembodiments, alleviation of one or more symptoms of bacterial vaginosisoccurs within about 21 to about 30 days after administration to thesubject.

In some embodiments, a method of reducing the incidence and/or risk of apreterm birth in a subject further comprises a resolution of one or moresymptoms of bacterial vaginosis within up to about seven days afteradministration to the subject. In some embodiments, a method of treatingbacterial vaginosis further comprises a resolution of one or moresymptoms of bacterial vaginosis within up to about seven days afteradministration to the subject. In some embodiments, the one or moresymptoms include, but are not limited to, abnormal vaginal odor,abnormal vaginal discharge or a combination thereof. In someembodiments, resolution of one or more symptoms of bacterial vaginosisoccurs within about 24 hours after administration to the subject. Insome embodiments, resolution of one or more symptoms of bacterialvaginosis occurs within about 48 hours after administration. In someembodiments, resolution of one or more symptoms of bacterial vaginosisoccurs within about 72 hours after administration to the subject. Insome embodiments, resolution of one or more symptoms of bacterialvaginosis occurs within about 96 hours after administration to thesubject. In some embodiments, resolution of one or more symptoms ofbacterial vaginosis occurs within about 120 hours after administrationto the subject. In some embodiments, resolution of one or more symptomsof bacterial vaginosis occurs within about 168 hours afteradministration to the subject. In some embodiments, resolution of one ormore symptoms of bacterial vaginosis occurs within about 7 to about 10days after administration to the subject. In some embodiments,resolution of one or more symptoms of bacterial vaginosis occurs withinabout 11 to about 20 days after administration to the subject. In someembodiments, resolution of one or more symptoms of bacterial vaginosisoccurs within about 21 to about 30 days after administration to thesubject.

Some embodiments are directed to a method of reducing the incidenceand/or risk of a subject transmitting human immunodeficiency virus (HIV)to a sexual partner. Bacterial vaginosis infections may increase therisk of a HIV transmission to sexual partner. In some embodiments, amethod of reducing the incidence and/or risk of the subject transmittingHIV to a sexual partner in a subject comprises administering to thesubject a therapeutically effective amount of secnidazole orpharmaceutically acceptable salts thereof. In some embodiments, a methodof reducing the incidence and/or risk of a preterm birth in a subjectcomprises administering to the subject a therapeutically effectiveamount of secnidazole or pharmaceutically acceptable salts thereof in amicrogranule formulation. In some embodiments, the secnidazolemicrogranule formulation may be suitable for oral administration. Insome embodiments, the secnidazole microgranule formulation comprises aplurality of microgranules. In some embodiments, the plurality ofmicrogranules are white to off-white in color. In some embodiments, theplurality of microgranules each have a particle size range of about 400micrometers to about 841 micrometers. In some embodiments, thesecnidazole microgranule formulation may be mixed, stirred, or otherwiseintegrated into a food substance. In some embodiments, the foodsubstance may be a semisolid or soft food. In some embodiments, the foodsubstance may include, but is not limited to applesauce, pudding, yogurtor the like. In some embodiments, integration of the secnidazolemicrogranule formulation into a food substance has a taste maskingfunction.

In some embodiments, the subject is a human female. In some embodiments,the subject is a female. In some embodiments, the subject is anotherwise healthy female. In some embodiments, the subject is a femalewith HIV. In some embodiments, the subject is an otherwise healthypregnant female. In some embodiments, the subject is a female having had3 or fewer bacterial vaginosis infections in the past 12 months. In someembodiments, the subject is a female having had 4 or more bacterialvaginosis infections in the past twelve months. In some embodiments, thesubject is a female with recurring bacterial vaginosis. In someembodiments, a subject with recurring bacterial vaginosis is a subjectwith 4 or more bacterial vaginosis infections within a twelve-monthperiod. In some embodiments, the subject is a female with frequentbacterial vaginosis infections. In some embodiments, a female withfrequent bacterial vaginosis infections is a female with 4 or morebacterial vaginosis infections within a twelve-month period. In someembodiments, the subject is a female presenting with an off-white (milkyor gray), thin, homogeneous vaginal discharge, vaginal pH greater thanor equal to 4.7, presence of clue cells of greater than or equal to 20%of the total epithelial cells on microscopic examination of a vaginalsaline wet mount, a positive 10% KOH Whiff test or a combinationthereof. In some embodiments, the subject is a female presenting with anoff-white (milky or gray), thin, homogeneous vaginal discharge, vaginalpH greater than or equal to 4.7, the presence of clue cells of greaterthan or equal to 20% of the total epithelial cells on microscopicexamination of a vaginal saline wet mount, and a positive 10% KOH Whifftest. In some embodiments, the subject is a female with confirmedbacterial vaginosis. In some embodiments, bacterial vaginosis isconfirmed by the presence of four (4) Amsel criteria parameters selectedfrom an off-white (milky or gray), thin, homogeneous vaginal discharge,vaginal pH greater than or equal to 4.7, the presence of clue cells ofgreater than or equal to 20% of the total epithelial cells onmicroscopic examination of a vaginal saline wet mount, a positive 10%KOH Whiff test and a gram stain slide Nugent score equal to, or higherthan four (4) on bacterial analysis of vaginal samples. In someembodiments, the subject is a female with suspected bacterial vaginosis.In some embodiments, suspected bacterial vaginosis is indicated by thepresence of four (4) Amsel criteria parameters selected from anoff-white (milky or gray), thin, homogeneous vaginal discharge, vaginalpH greater than or equal to 4.7, the presence of clue cells of greaterthan or equal to 20% of the total epithelial cells on microscopicexamination of a vaginal saline wet mount, and a positive 10% KOH Whifftest. In some embodiments, the subject is a female presenting with anoff-white (milky or gray), thin, homogeneous vaginal discharge, odor, ora combination thereof.

In some embodiments, a method of reducing the incidence and/or risk of asubject transmitting HIV to a sexual partner in a subject comprisesadministering to the subject a single dose of a therapeuticallyeffective amount of secnidazole in a microgranule formulation, whereinthe secnidazole comprises about 1 g to about 2 g of the microgranuleformulation. In some embodiments, the secnidazole microgranuleformulation is co-administered with an additional compound selected fromethinyl estradiol (EE2), norethindrone (NET), or a combination thereof.In some embodiments, the secnidazole microgranule formulation is mixedinto a semisolid or soft food substance, such as but not limited toapplesauce yogurt and pudding. In some embodiments, the amount of thefood substance is about 4-6 ounces.

In some embodiments, a method of reducing the incidence and/or risk of asubject transmitting HIV to a sexual partner in a subject comprisesadministering to the subject a single dose of a secnidazole microgranuleformulation that exhibits a maximum plasma concentration (C_(max)) ofbetween about 34.5 μg/ml and about 58.3 μg/ml. In some embodiments, amethod of treating bacterial vaginosis in a subject comprisesadministering to the subject a single dose of a secnidazole microgranuleformulation that exhibits a maximum plasma concentration (C_(max)) ofbetween about 17.4 μg/ml and about 26.5 μg/ml.

In some embodiments, a method of reducing the incidence and/or risk of asubject transmitting HIV to a sexual partner in a subject comprisesadministering to the subject a single dose of a secnidazole microgranuleformulation that exhibits a time to maximum plasma concentration(T_(max)) of about 3 hours to about 4.05 hours. In some embodiments, amethod of treating bacterial vaginosis in a subject comprisesadministering to the subject a single dose of a secnidazole microgranuleformulation that exhibits a time to maximum plasma concentration(T_(max)) of about 2 hours to about 6 hours.

In some embodiments, a method of reducing the incidence and/or risk of asubject transmitting HIV to a sexual partner in a subject furthercomprises the absence of HIV transmission. In some embodiments, a methodof reducing the incidence and/or risk of a subject transmitting humanimmunodeficiency virus (HIV) to a sexual partner in a subject furthercomprises determining a post treatment clinical outcome. In someembodiments, a post treatment clinical outcome is indicative of aclinical outcome responder. Some embodiments further comprisedetermining a post-treatment clinical outcome. In some embodiments, apost-treatment clinical outcome of clinical cure is defined as aclinical outcome responder. In some embodiments, a clinical outcomeresponder is a subject with normal vaginal discharge, a negative KOHWhiff test, and clue cells less than or equal to 20% of the totalepithelial cells on microscopic examination of a vaginal saline wetmount after treatment with a microgranule formulation comprising about 1to about 2 grams of secnidazole. In some embodiments, a clinical outcomeresponder has a gram stain slide Nugent score of less than four (4)after treatment with a single dose of secnidazole. In yet otherembodiments, a clinical outcome responder is a subject with normalvaginal discharge, a negative KOH Whiff test, clue cells less than 20%of total epithelial cells, and a gram stain slide Nugent score of lessthan four (4) after treatment with a single dose of secnidazole. In someembodiments, a clinical outcome responder has a gram stain slide Nugentscore of less than four (4) after treatment with a 2 gram single dose ofsecnidazole. In yet other embodiments, a clinical outcome responder is asubject with normal vaginal discharge, a negative KOH Whiff test, cluecells less than 20% of total epithelial cells, and a gram stain slideNugent score of less than four (4) after treatment with a 2 gram singledose of secnidazole. In some embodiments, a post-treatment clinicaloutcome is observable after about 24 hours after administration. In someembodiments, a post-treatment clinical outcome is observable after about48 hours after administration. In some embodiments, a post-treatmentclinical outcome is observable after about 72 hours afteradministration. In some embodiments, a post-treatment clinical outcomeis observable after about 96 hours after administration. In someembodiments, a post-treatment clinical outcome is observable after about120 hours after administration. In some embodiments, a post-treatmentclinical outcome is observable after about 168 hours afteradministration. In some embodiments, a post-treatment clinical outcomeis observable after about 7 to about 10 days after administration. Insome embodiments, a post-treatment clinical outcome is observable afterabout 11 to about 20 days after administration. In some embodiments, apost-treatment clinical outcome is observable after about 21 to about 30days after administration.

In some embodiments, a method of reducing the incidence and/or risk of asubject transmitting HIV to a sexual partner in a subject furthercomprises an alleviation of one or more symptoms of bacterial vaginosiswithin up to about three days after administration to the subject. Insome embodiments, a method of treating bacterial vaginosis furthercomprises an alleviation of one or more symptoms of bacterial vaginosiswithin up to about three days after administration to the subject. Insome embodiments, the one or more symptoms include, but are not limitedto, abnormal vaginal odor, abnormal vaginal discharge or a combinationthereof. In some embodiments, alleviation refers to a lessening of theseverity of one or more symptoms. In some embodiments, alleviation ofone or more symptoms of bacterial vaginosis occurs within about 24 hoursafter administration. In some embodiments, alleviation of one or moresymptoms of bacterial vaginosis occurs within about 48 hours afteradministration. In some embodiments, alleviation of one or more symptomsof bacterial vaginosis occurs within about 72 hours after administrationto the subject. In some embodiments, alleviation of one or more symptomsof bacterial vaginosis occurs within about 96 hours after administrationto the subject. In some embodiments, alleviation of one or more symptomsof bacterial vaginosis occurs within about 120 hours afteradministration to the subject. In some embodiments, alleviation of oneor more symptoms of bacterial vaginosis occurs within about 168 hoursafter administration to the subject. In some embodiments, alleviation ofone or more symptoms of bacterial vaginosis occurs within about 7 toabout 10 days after administration to the subject. In some embodiments,alleviation of one or more symptoms of bacterial vaginosis occurs withinabout 11 to about 20 days after administration to the subject. In someembodiments, alleviation of one or more symptoms of bacterial vaginosisoccurs within about 21 to about 30 days after administration to thesubject.

In some embodiments, a method of reducing the incidence and/or risk of asubject transmitting HIV to a sexual partner a subject further comprisesa resolution of one or more symptoms of bacterial vaginosis within up toabout seven days after administration to the subject. In someembodiments, a method of treating bacterial vaginosis further comprisesa resolution of one or more symptoms of bacterial vaginosis within up toabout seven days after administration to the subject. In someembodiments, the one or more symptoms include, but are not limited to,abnormal vaginal odor, abnormal vaginal discharge or a combinationthereof. In some embodiments, resolution of one or more symptoms ofbacterial vaginosis occurs within about 24 hours after administration tothe subject. In some embodiments, resolution of one or more symptoms ofbacterial vaginosis occurs within about 48 hours after administration.In some embodiments, resolution of one or more symptoms of bacterialvaginosis occurs within about 72 hours after administration to thesubject. In some embodiments, resolution of one or more symptoms ofbacterial vaginosis occurs within about 96 hours after administration tothe subject. In some embodiments, resolution of one or more symptoms ofbacterial vaginosis occurs within about 120 hours after administrationto the subject. In some embodiments, resolution of one or more symptomsof bacterial vaginosis occurs within about 168 hours afteradministration to the subject. In some embodiments, resolution of one ormore symptoms of bacterial vaginosis occurs within about 7 to about 10days after administration to the subject. In some embodiments,resolution of one or more symptoms of bacterial vaginosis occurs withinabout 11 to about 20 days after administration to the subject. In someembodiments, resolution of one or more symptoms of bacterial vaginosisoccurs within about 21 to about 30 days after administration to thesubject.

Some embodiments are directed to a method of reducing the incidenceand/or risk of a subject acquiring HIV from a sexual partner. Bacterialvaginosis infections may increase the risk of a HIV transmission tosexual partner as well as the risk of acquiring HIV from a sexualpartner. In some embodiments, a method of reducing the incidence and/orrisk of the subject transmitting HIV to a sexual partner comprisesadministering to the subject a therapeutically effective amount ofsecnidazole or pharmaceutically acceptable salts thereof. In someembodiments, a method of reducing the incidence and/or risk of a pretermbirth in a subject comprises administering to the subject atherapeutically effective amount of secnidazole or pharmaceuticallyacceptable salts thereof in a microgranule formulation. In someembodiments, the secnidazole microgranule formulation may be suitablefor oral administration. In some embodiments, the secnidazolemicrogranule formulation comprises a plurality of microgranules. In someembodiments, the plurality of microgranules are white to off-white incolor. In some embodiments, the plurality of microgranules each have aparticle size range of about 400 micrometers to about 841 micrometers.In some embodiments, the secnidazole microgranule formulation may bemixed, stirred, or otherwise integrated into a food substance. In someembodiments, the food substance may be a semisolid or soft food. In someembodiments, the food substance may include, but is not limited toapplesauce, pudding, yogurt or the like. In some embodiments,integration of the secnidazole microgranule formulation into a foodsubstance has a taste masking function.

In some embodiments, the subject is a human. In yet other embodiments,the subject is a pregnant human female. In some embodiments, the subjectis an otherwise healthy female. In some embodiments, the subject is afemale without HIV. In some embodiments, the subject has a sexualpartner that is HIV positive. In some embodiments, the subject is anotherwise healthy pregnant female. In some embodiments, the subject is afemale having had 3 or fewer bacterial vaginosis infections in the past12 months. In some embodiments, the subject is a female having had 4 ormore bacterial vaginosis infections in the past twelve months. In someembodiments, the subject is a female with recurring bacterial vaginosis.In some embodiments, a subject with recurring bacterial vaginosis is asubject with 4 or more bacterial vaginosis infections within atwelve-month period. In some embodiments, the subject is a female withfrequent bacterial vaginosis infections. In some embodiments, a femalewith frequent bacterial vaginosis infections is a female with 4 or morebacterial vaginosis infections within a twelve-month period. In someembodiments, the subject is a female presenting with an off-white (milkyor gray), thin, homogeneous vaginal discharge, vaginal pH greater thanor equal to 4.7, presence of clue cells of greater than or equal to 20%of the total epithelial cells on microscopic examination of a vaginalsaline wet mount, a positive 10% KOH Whiff test or a combinationthereof. In some embodiments, the subject is a female presenting with anoff-white (milky or gray), thin, homogeneous vaginal discharge, vaginalpH greater than or equal to 4.7, the presence of clue cells of greaterthan or equal to 20% of the total epithelial cells on microscopicexamination of a vaginal saline wet mount, and a positive 10% KOH Whifftest. In some embodiments, the subject is a female with confirmedbacterial vaginosis. In some embodiments, bacterial vaginosis isconfirmed by the presence of four (4) Amsel criteria parameters selectedfrom an off-white (milky or gray), thin, homogeneous vaginal discharge,vaginal pH greater than or equal to 4.7, the presence of clue cells ofgreater than or equal to 20% of the total epithelial cells onmicroscopic examination of a vaginal saline wet mount, a positive 10%KOH Whiff test and a gram stain slide Nugent score equal to, or higherthan four (4) on bacterial analysis of vaginal samples. In someembodiments, the subject is a female with suspected bacterial vaginosis.In some embodiments, suspected bacterial vaginosis is indicated by thepresence of four (4) Amsel criteria parameters selected from anoff-white (milky or gray), thin, homogeneous vaginal discharge, vaginalpH greater than or equal to 4.7, the presence of clue cells of greaterthan or equal to 20% of the total epithelial cells on microscopicexamination of a vaginal saline wet mount, and a positive 10% KOH Whifftest. In some embodiments, the subject is a female presenting with anoff-white (milky or gray), thin, homogeneous vaginal discharge, odor, ora combination thereof.

In some embodiments, a method of reducing the incidence and/or risk of asubject acquiring HIV from a sexual partner comprises administering tothe subject a single dose of a therapeutically effective amount ofsecnidazole in a microgranule formulation, wherein the secnidazolecomprises about 1 g to about 2 g of the microgranule formulation. Insome embodiments, the secnidazole microgranule formulation isco-administered with an additional compound selected from ethinylestradiol (EE2), norethindrone (NET), or a combination thereof. In someembodiments, the secnidazole microgranule formulation is mixed into asemisolid or soft food substance, such as but not limited to applesauceyogurt and pudding. In some embodiments, the amount of the foodsubstance is about 4-6 ounces.

In some embodiments, a method of reducing the incidence and/or risk of asubject acquiring HIV from a sexual partner comprises administering tothe subject a single dose of a secnidazole microgranule formulation thatexhibits a maximum plasma concentration (C_(max)) of between about 34.5μg/ml and about 58.3 μg/ml. In some embodiments, a method of treatingbacterial vaginosis in a subject comprises administering to the subjecta single dose of a secnidazole microgranule formulation that exhibits amaximum plasma concentration (C_(max)) of between about 17.4 μg/ml andabout 26.5 μg/ml.

In some embodiments, a method of reducing the incidence and/or risk of asubject acquiring HIV from a sexual partner comprises administering tothe subject a single dose of a secnidazole microgranule formulation thatexhibits a time to maximum plasma concentration (T_(max)) of about 3hours to about 4.05 hours. In some embodiments, a method of treatingbacterial vaginosis in a subject comprises administering to the subjecta single dose of a secnidazole microgranule formulation that exhibits atime to maximum plasma concentration (T_(max)) of about 2 hours to about6 hours.

In some embodiments, a method of reducing the incidence and/or risk of asubject acquiring HIV from a sexual partner in a subject furthercomprises the absence of HIV transmission. In some embodiments, a methodof reducing the incidence and/or risk of a subject transmitting humanimmunodeficiency virus (HIV) to a sexual partner in a subject furthercomprises determining a post treatment clinical outcome. In someembodiments, a post treatment clinical outcome is indicative of aclinical outcome responder. Some embodiments further comprisedetermining a post-treatment clinical outcome. In some embodiments, apost-treatment clinical outcome of clinical cure is defined as aclinical outcome responder. In some embodiments, a clinical outcomeresponder is a subject with normal vaginal discharge, a negative KOHWhiff test, and clue cells less than or equal to 20% of the totalepithelial cells on microscopic examination of a vaginal saline wetmount after treatment with a microgranule formulation comprising about 1to about 2 grams of secnidazole. In some embodiments, a clinical outcomeresponder has a gram stain slide Nugent score of less than four (4)after treatment with a single dose of secnidazole. In yet otherembodiments, a clinical outcome responder is a subject with normalvaginal discharge, a negative KOH Whiff test, clue cells less than 20%of total epithelial cells, and a gram stain slide Nugent score of lessthan four (4) after treatment with a single dose of secnidazole. In someembodiments, a clinical outcome responder has a gram stain slide Nugentscore of less than four (4) after treatment with a 2 gram single dose ofsecnidazole. In yet other embodiments, a clinical outcome responder is asubject with normal vaginal discharge, a negative KOH Whiff test, cluecells less than 20% of total epithelial cells, and a gram stain slideNugent score of less than four (4) after treatment with a 2 gram singledose of secnidazole. In some embodiments, a post-treatment clinicaloutcome is observable after about 24 hours after administration. In someembodiments, a post-treatment clinical outcome is observable after about48 hours after administration. In some embodiments, a post-treatmentclinical outcome is observable after about 72 hours afteradministration. In some embodiments, a post-treatment clinical outcomeis observable after about 96 hours after administration. In someembodiments, a post-treatment clinical outcome is observable after about120 hours after administration. In some embodiments, a post-treatmentclinical outcome is observable after about 168 hours afteradministration. In some embodiments, a post-treatment clinical outcomeis observable after about 7 to about 10 days after administration. Insome embodiments, a post-treatment clinical outcome is observable afterabout 11 to about 20 days after administration. In some embodiments, apost-treatment clinical outcome is observable after about 21 to about 30days after administration.

In some embodiments, a method of reducing the incidence and/or risk of asubject acquiring HIV from a sexual partner further comprises analleviation of one or more symptoms of bacterial vaginosis within up toabout three days after administration to the subject. In someembodiments, a method of treating bacterial vaginosis further comprisesan alleviation of one or more symptoms of bacterial vaginosis within upto about three days after administration to the subject. In someembodiments, the one or more symptoms include, but are not limited to,abnormal vaginal odor, abnormal vaginal discharge or a combinationthereof. In some embodiments, alleviation refers to a lessening of theseverity of one or more symptoms. In some embodiments, alleviation ofone or more symptoms of bacterial vaginosis occurs within about 24 hoursafter administration. In some embodiments, alleviation of one or moresymptoms of bacterial vaginosis occurs within about 48 hours afteradministration. In some embodiments, alleviation of one or more symptomsof bacterial vaginosis occurs within about 72 hours after administrationto the subject. In some embodiments, alleviation of one or more symptomsof bacterial vaginosis occurs within about 96 hours after administrationto the subject. In some embodiments, alleviation of one or more symptomsof bacterial vaginosis occurs within about 120 hours afteradministration to the subject. In some embodiments, alleviation of oneor more symptoms of bacterial vaginosis occurs within about 168 hoursafter administration to the subject. In some embodiments, alleviation ofone or more symptoms of bacterial vaginosis occurs within about 7 toabout 10 days after administration to the subject. In some embodiments,alleviation of one or more symptoms of bacterial vaginosis occurs withinabout 11 to about 20 days after administration to the subject. In someembodiments, alleviation of one or more symptoms of bacterial vaginosisoccurs within about 21 to about 30 days after administration to thesubject.

In some embodiments, a method of reducing the incidence and/or risk of asubject acquiring HIV from a sexual partner further comprises aresolution of one or more symptoms of bacterial vaginosis within up toabout seven days after administration to the subject. In someembodiments, a method of treating bacterial vaginosis further comprisesa resolution of one or more symptoms of bacterial vaginosis within up toabout seven days after administration to the subject. In someembodiments, the one or more symptoms include, but are not limited to,abnormal vaginal odor, abnormal vaginal discharge or a combinationthereof. In some embodiments, resolution of one or more symptoms ofbacterial vaginosis occurs within about 24 hours after administration tothe subject. In some embodiments, resolution of one or more symptoms ofbacterial vaginosis occurs within about 48 hours after administration.In some embodiments, resolution of one or more symptoms of bacterialvaginosis occurs within about 72 hours after administration to thesubject. In some embodiments, resolution of one or more symptoms ofbacterial vaginosis occurs within about 96 hours after administration tothe subject. In some embodiments, resolution of one or more symptoms ofbacterial vaginosis occurs within about 120 hours after administrationto the subject. In some embodiments, resolution of one or more symptomsof bacterial vaginosis occurs within about 168 hours afteradministration to the subject. In some embodiments, resolution of one ormore symptoms of bacterial vaginosis occurs within about 7 to about 10days after administration to the subject. In some embodiments,resolution of one or more symptoms of bacterial vaginosis occurs withinabout 11 to about 20 days after administration to the subject. In someembodiments, resolution of one or more symptoms of bacterial vaginosisoccurs within about 21 to about 30 days after administration to thesubject.

Some embodiments are directed to a method of reducing the incidenceand/or risk of a subject acquiring a sexually transmitted infection(STI) from a sexual partner. Bacterial vaginosis infections may increasethe risk of acquiring an STI from a sexual partner. In some embodiments,STI's include, but are not limited to chlamydia, gonorrhea,trichomoniasis, HSV-2, and HPV. In some embodiments, a method ofreducing the incidence and/or risk of the subject transmitting HIV to asexual partner in a subject comprises administering to the subject atherapeutically effective amount of secnidazole or pharmaceuticallyacceptable salts thereof. In some embodiments, a method of reducing theincidence and/or risk of a preterm birth in a subject comprisesadministering to the subject a therapeutically effective amount ofsecnidazole or pharmaceutically acceptable salts thereof in amicrogranule formulation. In some embodiments, the secnidazolemicrogranule formulation may be suitable for oral administration. Insome embodiments, the secnidazole microgranule formulation comprises aplurality of microgranules. In some embodiments, the plurality ofmicrogranules are white to off-white in color. In some embodiments, theplurality of microgranules each have a particle size range of about 400micrometers to about 841 micrometers. In some embodiments, thesecnidazole microgranule formulation may be mixed, stirred, or otherwiseintegrated into a food substance. In some embodiments, the foodsubstance may be a semisolid or soft food. In some embodiments, the foodsubstance may include, but is not limited to applesauce, pudding, yogurtor the like. In some embodiments, integration of the secnidazolemicrogranule formulation into a food substance has a taste maskingfunction.

In some embodiments, the subject is a human. In yet other embodiments,the subject is a pregnant human female. In some embodiments, the subjectis an otherwise healthy female. In some embodiments, the subject is afemale with an STI. In some embodiments, the subject is a female havinghad 3 or fewer bacterial vaginosis infections in the past 12 months. Insome embodiments, the subject is a female having had 4 or more bacterialvaginosis infections in the past twelve months. In some embodiments, thesubject is a female with recurring bacterial vaginosis. In someembodiments, a subject with recurring bacterial vaginosis is a subjectwith 4 or more bacterial vaginosis infections within a twelve-monthperiod. In some embodiments, the subject is a female with frequentbacterial vaginosis infections. In some embodiments, a female withfrequent bacterial vaginosis infections is a female with 4 or morebacterial vaginosis infections within a twelve-month period. In someembodiments, the subject is a female presenting with an off-white (milkyor gray), thin, homogeneous vaginal discharge, vaginal pH greater thanor equal to 4.7, presence of clue cells of greater than or equal to 20%of the total epithelial cells on microscopic examination of a vaginalsaline wet mount, a positive 10% KOH Whiff test or a combinationthereof. In some embodiments, the subject is a female presenting with anoff-white (milky or gray), thin, homogeneous vaginal discharge, vaginalpH greater than or equal to 4.7, the presence of clue cells of greaterthan or equal to 20% of the total epithelial cells on microscopicexamination of a vaginal saline wet mount, and a positive 10% KOH Whifftest. In some embodiments, the subject is a female with confirmedbacterial vaginosis. In some embodiments, bacterial vaginosis isconfirmed by the presence of four (4) Amsel criteria parameters selectedfrom an off-white (milky or gray), thin, homogeneous vaginal discharge,vaginal pH greater than or equal to 4.7, the presence of clue cells ofgreater than or equal to 20% of the total epithelial cells onmicroscopic examination of a vaginal saline wet mount, a positive 10%KOH Whiff test and a gram stain slide Nugent score equal to, or higherthan four (4) on bacterial analysis of vaginal samples. In someembodiments, the subject is a female with suspected bacterial vaginosis.In some embodiments, suspected bacterial vaginosis is indicated by thepresence of four (4) Amsel criteria parameters selected from anoff-white (milky or gray), thin, homogeneous vaginal discharge, vaginalpH greater than or equal to 4.7, the presence of clue cells of greaterthan or equal to 20% of the total epithelial cells on microscopicexamination of a vaginal saline wet mount, and a positive 10% KOH Whifftest. In some embodiments, the subject is a female presenting with anoff-white (milky or gray), thin, homogeneous vaginal discharge, odor, ora combination thereof.

In some embodiments, a method of reducing the incidence and/or risk of asubject acquiring an STI from a sexual partner comprises administeringto the subject a single dose of a therapeutically effective amount ofsecnidazole in a microgranule formulation, wherein the secnidazolecomprises about 1 g to about 2 g of the microgranule formulation. Insome embodiments, the secnidazole microgranule formulation isco-administered with an additional compound selected from ethinylestradiol (EE2), norethindrone (NET), or a combination thereof. In someembodiments, the secnidazole microgranule formulation is mixed into asemisolid or soft food substance, such as but not limited to applesauceyogurt and pudding. In some embodiments, the amount of the foodsubstance is about 4-6 ounces.

In some embodiments, a method of reducing the incidence and/or risk of asubject acquiring an STI from a sexual partner comprises administeringto the subject a single dose of a secnidazole microgranule formulationthat exhibits a maximum plasma concentration (C_(max)) of between about34.5 μg/ml and about 58.3 μg/ml. In some embodiments, a method oftreating bacterial vaginosis in a subject comprises administering to thesubject a single dose of a secnidazole microgranule formulation thatexhibits a maximum plasma concentration (C_(max)) of between about 17.4μg/ml and about 26.5 μg/ml.

In some embodiments, a method of reducing the incidence and/or risk of asubject acquiring an STI from a sexual partner comprises administeringto the subject a single dose of a secnidazole microgranule formulationthat exhibits a time to maximum plasma concentration (T_(max)) of about3 hours to about 4.05 hours. In some embodiments, a method of treatingbacterial vaginosis in a subject comprises administering to the subjecta single dose of a secnidazole microgranule formulation that exhibits atime to maximum plasma concentration (T_(max)) of about 2 hours to about6 hours.

In some embodiments, a method of reducing the incidence and/or risk of asubject acquiring an STI from a sexual partner further comprises theabsence of an STI transmission or acquisition of an STI by the subject.In some embodiments, a method of reducing the incidence and/or risk of asubject acquiring an STI from a sexual partner further comprisesdetermining a post treatment clinical outcome. In some embodiments, apost treatment clinical outcome is indicative of a clinical outcomeresponder. Some embodiments further comprise determining apost-treatment clinical outcome. In some embodiments, a post-treatmentclinical outcome of clinical cure is defined as a clinical outcomeresponder. In some embodiments, a clinical outcome responder is asubject with normal vaginal discharge, a negative KOH Whiff test, andclue cells less than or equal to 20% of the total epithelial cells onmicroscopic examination of a vaginal saline wet mount after treatmentwith a microgranule formulation comprising about 1 to about 2 grams ofsecnidazole. In some embodiments, a clinical outcome responder has agram stain slide Nugent score of less than four (4) after treatment witha single dose of secnidazole. In yet other embodiments, a clinicaloutcome responder is a subject with normal vaginal discharge, a negativeKOH Whiff test, clue cells less than 20% of total epithelial cells, anda gram stain slide Nugent score of less than four (4) after treatmentwith a single dose of secnidazole. In some embodiments, a clinicaloutcome responder has a gram stain slide Nugent score of less than four(4) after treatment with a 2 gram single dose of secnidazole. In yetother embodiments, a clinical outcome responder is a subject with normalvaginal discharge, a negative KOH Whiff test, clue cells less than 20%of total epithelial cells, and a gram stain slide Nugent score of lessthan four (4) after treatment with a 2 gram single dose of secnidazole.In some embodiments, a post-treatment clinical outcome is observableafter about 24 hours after administration. In some embodiments, apost-treatment clinical outcome is observable after about 48 hours afteradministration. In some embodiments, a post-treatment clinical outcomeis observable after about 72 hours after administration. In someembodiments, a post-treatment clinical outcome is observable after about96 hours after administration. In some embodiments, a post-treatmentclinical outcome is observable after about 120 hours afteradministration. In some embodiments, a post-treatment clinical outcomeis observable after about 168 hours after administration. In someembodiments, a post-treatment clinical outcome is observable after about7 to about 10 days after administration. In some embodiments, apost-treatment clinical outcome is observable after about 11 to about 20days after administration. In some embodiments, a post-treatmentclinical outcome is observable after about 21 to about 30 days afteradministration.

In some embodiments, a method of reducing the incidence and/or risk of asubject acquiring an STI from a sexual partner further comprises analleviation of one or more symptoms of bacterial vaginosis within up toabout three days after administration to the subject. In someembodiments, a method of treating bacterial vaginosis further comprisesan alleviation of one or more symptoms of bacterial vaginosis within upto about three days after administration to the subject. In someembodiments, the one or more symptoms include, but are not limited to,abnormal vaginal odor, abnormal vaginal discharge or a combinationthereof. In some embodiments, alleviation refers to a lessening of theseverity of one or more symptoms. In some embodiments, alleviation ofone or more symptoms of bacterial vaginosis occurs within about 24 hoursafter administration. In some embodiments, alleviation of one or moresymptoms of bacterial vaginosis occurs within about 48 hours afteradministration. In some embodiments, alleviation of one or more symptomsof bacterial vaginosis occurs within about 72 hours after administrationto the subject. In some embodiments, alleviation of one or more symptomsof bacterial vaginosis occurs within about 96 hours after administrationto the subject. In some embodiments, alleviation of one or more symptomsof bacterial vaginosis occurs within about 120 hours afteradministration to the subject. In some embodiments, alleviation of oneor more symptoms of bacterial vaginosis occurs within about 168 hoursafter administration to the subject. In some embodiments, alleviation ofone or more symptoms of bacterial vaginosis occurs within about 7 toabout 10 days after administration to the subject. In some embodiments,alleviation of one or more symptoms of bacterial vaginosis occurs withinabout 11 to about 20 days after administration to the subject. In someembodiments, alleviation of one or more symptoms of bacterial vaginosisoccurs within about 21 to about 30 days after administration to thesubject.

In some embodiments, a method of reducing the incidence and/or risk of asubject acquiring an STI from a sexual partner further comprises aresolution of one or more symptoms of bacterial vaginosis within up toabout seven days after administration to the subject. In someembodiments, a method of treating bacterial vaginosis further comprisesa resolution of one or more symptoms of bacterial vaginosis within up toabout seven days after administration to the subject. In someembodiments, the one or more symptoms include, but are not limited to,abnormal vaginal odor, abnormal vaginal discharge or a combinationthereof. In some embodiments, resolution of one or more symptoms ofbacterial vaginosis occurs within about 24 hours after administration tothe subject. In some embodiments, resolution of one or more symptoms ofbacterial vaginosis occurs within about 48 hours after administration.In some embodiments, resolution of one or more symptoms of bacterialvaginosis occurs within about 72 hours after administration to thesubject. In some embodiments, resolution of one or more symptoms ofbacterial vaginosis occurs within about 96 hours after administration tothe subject. In some embodiments, resolution of one or more symptoms ofbacterial vaginosis occurs within about 120 hours after administrationto the subject. In some embodiments, resolution of one or more symptomsof bacterial vaginosis occurs within about 168 hours afteradministration to the subject. In some embodiments, resolution of one ormore symptoms of bacterial vaginosis occurs within about 7 to about 10days after administration to the subject. In some embodiments,resolution of one or more symptoms of bacterial vaginosis occurs withinabout 11 to about 20 days after administration to the subject. In someembodiments, resolution of one or more symptoms of bacterial vaginosisoccurs within about 21 to about 30 days after administration to thesubject.

Some embodiments are directed to a method of preventing recurrence ofbacterial vaginosis. In some embodiments, the method of preventingrecurrence of bacterial vaginosis comprises administering a microgranuleformulation comprising about 1 to about 2 grams secnidazole to a subjectin need thereof. In some embodiments, the recurrence of bacterialvaginosis is decreased after administration of a single, 2 gram dose ofsecnidazole. In some embodiments, the recurrence of bacterial vaginosisis decreased after administration of a multiple, 2 gram doses ofsecnidazole. In some embodiments, multiple doses may be given atpre-determined intervals such as but not limited to once a week,bi-weekly, monthly, bimonthly for the duration of treatment. In someembodiment, the duration of treatment may be at least one week. In someembodiment, the duration of treatment may be at least one month. In someembodiments, the duration of treatment is about six months. Someembodiments are directed to a method of preventing recurrence ofbacterial vaginosis comprising administering a microgranule formulationcomprising about 2 grams secnidazole, to a subject in need thereof. Insome embodiments, the microgranule formulation comprising about 2 gramssecnidazole is administered as a single dose. In some embodiments, thesingle dose of secnidazole is the only dose need to prevent recurrenceof bacterial vaginosis. In some embodiments, the microgranuleformulation comprising about 2 grams secnidazole is administered inmultiple doses. In some embodiments, multiple doses may be given atpre-determined intervals such as but not limited to once a week,bi-weekly, monthly, bimonthly for the duration of treatment. In someembodiment, the duration of treatment may be at least one week. In someembodiment, the duration of treatment may be at least one month. In someembodiments, the duration of treatment is about six months.

In some embodiments, the method of preventing recurrence of bacterialvaginosis in a subject in need thereof comprises administering to thesubject a therapeutically effective amount of secnidazole orpharmaceutically acceptable salts thereof in a microgranule formulation.In some embodiments, the secnidazole microgranule formulation may besuitable for oral administration. In some embodiments, the secnidazolemicrogranule formulation comprises a plurality of microgranules. In someembodiments, the plurality of microgranules are white to off-white incolor. In some embodiments, the plurality of microgranules each have aparticle size range of about 400 micrometers to about 841 micrometers.In some embodiments, the secnidazole microgranule formulation may bemixed, stirred, or otherwise integrated into a food substance. In someembodiments, the food substance may be a semisolid or soft food. In someembodiments, the food substance may include, but is not limited toapplesauce, pudding, yogurt or the like. In some embodiments,integration of the secnidazole microgranule formulation into a foodsubstance has a taste masking function.

In some embodiments, the subject is a female. In some embodiments, thesubject is an otherwise healthy female. In some embodiments, the subjectis a pregnant female. In some embodiments, the subject is an otherwisehealthy pregnant female. In some embodiments, the subject is a femalehaving had 3 or fewer bacterial vaginosis infections in the past 12months. In some embodiments, the subject is a female having had 3 ormore bacterial vaginosis infections in the past 12 months. In someembodiments, the subject is a female having had 4 or more bacterialvaginosis infections in the past twelve months. In some embodiments, thesubject is a female with recurring bacterial vaginosis. In someembodiments, a subject with recurring bacterial vaginosis is a subjectwith 3 or more bacterial vaginosis infections within a twelve-monthperiod. In some embodiments, a subject with recurring bacterialvaginosis is a subject with 4 or more bacterial vaginosis infectionswithin a twelve-month period. In some embodiments, the subject is afemale with frequent bacterial vaginosis infections. In someembodiments, a female with frequent bacterial vaginosis infections is afemale with 4 or more bacterial vaginosis infections within atwelve-month period. In some embodiments, the subject is a femalepresenting with an off-white (milky or gray), thin, homogeneous vaginaldischarge, vaginal pH greater than or equal to 4.7, presence of cluecells of greater than or equal to 20% of the total epithelial cells onmicroscopic examination of a vaginal saline wet mount, a positive 10%KOH Whiff test or a combination thereof. In some embodiments, thesubject is a female presenting with an off-white (milky or gray), thin,homogeneous vaginal discharge, vaginal pH greater than or equal to 4.7,the presence of clue cells of greater than or equal to 20% of the totalepithelial cells on microscopic examination of a vaginal saline wetmount, and a positive 10% KOH Whiff test. In some embodiments, thesubject is a female with confirmed bacterial vaginosis. In someembodiments, bacterial vaginosis is confirmed by the presence of four(4) Amsel criteria parameters selected from an off-white (milky orgray), thin, homogeneous vaginal discharge, vaginal pH greater than orequal to 4.7, the presence of clue cells of greater than or equal to 20%of the total epithelial cells on microscopic examination of a vaginalsaline wet mount, a positive 10% KOH Whiff test and a gram stain slideNugent score equal to, or higher than four (4) on bacterial analysis ofvaginal samples. In some embodiments, the subject is a female withsuspected bacterial vaginosis. In some embodiments, suspected bacterialvaginosis is indicated by the presence of four (4) Amsel criteriaparameters selected from an off-white (milky or gray), thin, homogeneousvaginal discharge, vaginal pH greater than or equal to 4.7, the presenceof clue cells of greater than or equal to 20% of the total epithelialcells on microscopic examination of a vaginal saline wet mount, and apositive 10% KOH Whiff test. In some embodiments, the subject is afemale presenting with an off-white (milky or gray), thin, homogeneousvaginal discharge, odor, or a combination thereof.

In some embodiments, a method of preventing recurrence of bacterialvaginosis in a subject comprises administering to the subject a singledose of a therapeutically effective amount of secnidazole in amicrogranule formulation, wherein the secnidazole comprises about 1 g toabout 2 g of the microgranule formulation. In some embodiments, a methodof preventing recurrence of bacterial vaginosis in a subject comprisesadministering to the subject multiple doses of a therapeuticallyeffective amount of secnidazole in a microgranule formulation, whereinthe secnidazole comprises about 1 g to about 2 g of the microgranuleformulation. In some embodiments, multiple doses may be given atpre-determined intervals such as but not limited to once a week,bi-weekly, monthly, bimonthly for the duration of treatment. In someembodiment, the duration of treatment may be at least one week. In someembodiment, the duration of treatment may be at least one month. In someembodiments, the duration of treatment is about six months. In someembodiments, the secnidazole microgranule formulation is mixed into asemisolid or soft food substance, such as but not limited to applesauceyogurt and pudding. In some embodiments, the amount of the foodsubstance is about 4-6 ounces.

In some embodiments, a method of preventing recurrence of bacterialvaginosis in a subject comprises administering to the subject a singledose of a secnidazole microgranule formulation that exhibits a maximumplasma concentration (C_(max)) of between about 34.5 μg/ml and about58.3 μg/ml. In some embodiments, a method of preventing recurrence ofbacterial vaginosis in a subject comprises administering to the subjecta single dose of a secnidazole microgranule formulation that exhibits amaximum plasma concentration (C_(max)) of between about 17.4 μg/ml andabout 26.5 μg/ml. In some embodiments, a method of preventing recurrenceof bacterial vaginosis in a subject comprises administering to thesubject multiple doses of a secnidazole microgranule formulation whereineach dose exhibits a maximum plasma concentration (C_(max)) of betweenabout 34.5 μg/ml and about 58.3 μg/ml. In some embodiments, multipledoses may be given at pre-determined intervals such as but not limitedto once a week, bi-weekly, monthly, bimonthly for the duration oftreatment. In some embodiment, the duration of treatment may be at leastone week. In some embodiment, the duration of treatment may be at leastone month. In some embodiments, the duration of treatment is about sixmonths. In some embodiments, a method of preventing recurrence ofbacterial vaginosis in a subject comprises administering to the subjectmultiple doses of a secnidazole microgranule formulation wherein eachdose exhibits a maximum plasma concentration (C_(max)) of between about17.4 μg/ml and about 26.5 μg/ml. In some embodiments, multiple doses maybe given at pre-determined intervals such as but not limited to once aweek, bi-weekly, monthly, bimonthly for the duration of treatment. Insome embodiment, the duration of treatment may be at least one week. Insome embodiment, the duration of treatment may be at least one month. Insome embodiments, the duration of treatment is about six months.

In some embodiments, a method of preventing recurrence of bacterialvaginosis in a subject comprises administering to the subject a singledose of a secnidazole microgranule formulation that exhibits a time tomaximum plasma concentration (T_(max)) of about 3 hours to about 4.05hours. In some embodiments, a method of preventing recurrence ofbacterial vaginosis in a subject comprises administering to the subjecta single dose of a secnidazole microgranule formulation that exhibits atime to maximum plasma concentration (T_(max)) of about 2 hours to about6 hours. In some embodiments, a method of preventing recurrence ofbacterial vaginosis in a subject comprises administering to the subjectmultiple doses of a secnidazole microgranule formulation wherein asingle dose exhibits a time to maximum plasma concentration (T_(max)) ofabout 3 hours to about 4.05 hours. In some embodiments, a method ofpreventing recurrence of bacterial vaginosis in a subject comprisesadministering to the subject multiple doses of a secnidazolemicrogranule formulation wherein each dose exhibits a time to maximumplasma concentration (T_(max)) of about 2 hours to about 6 hours. Insome embodiments, multiple doses may be given at pre-determinedintervals such as but not limited to once a week, bi-weekly, monthly,bimonthly for the duration of treatment. In some embodiment, theduration of treatment may be at least one week. In some embodiment, theduration of treatment may be at least one month. In some embodiments,the duration of treatment is about six months.

In some embodiments, a method of preventing recurrence of bacterialvaginosis in a subject further comprises determining a post treatmentclinical outcome. In some embodiments, a post treatment clinical outcomeis indicative of a clinical outcome responder. Some embodiments furthercomprise determining a post-treatment clinical outcome. In someembodiments, a post-treatment clinical outcome of clinical cure isdefined as a clinical outcome responder. In some embodiments, a clinicaloutcome responder is a subject with normal vaginal discharge, a negativeKOH Whiff test, and clue cells less than or equal to 20% of the totalepithelial cells on microscopic examination of a vaginal saline wetmount after treatment with an oral microgranule formulation comprisingabout 1 to about 2 grams of secnidazole. In some embodiments, a clinicaloutcome responder has a gram stain slide Nugent score of less than four(4) after treatment with a single dose of secnidazole. In yet otherembodiments, a clinical outcome responder is a subject with normalvaginal discharge, a negative KOH Whiff test, clue cells less than 20%of total epithelial cells, and a gram stain slide Nugent score of lessthan four (4) after treatment with a single dose of secnidazole. In someembodiments, a clinical outcome responder has a gram stain slide Nugentscore of less than four (4) after treatment with a 2 gram single dose ofsecnidazole. In yet other embodiments, a clinical outcome responder is asubject with normal vaginal discharge, a negative KOH Whiff test, cluecells less than 20% of total epithelial cells, and a gram stain slideNugent score of less than four (4) after treatment with a 2 gram singledose of secnidazole. In some embodiments, a post-treatment clinicaloutcome is observable after about 24 hours after administration. In someembodiments, a post-treatment clinical outcome is observable after about48 hours after administration. In some embodiments, a post-treatmentclinical outcome is observable after about 72 hours afteradministration. In some embodiments, a post-treatment clinical outcomeis observable after about 96 hours after administration. In someembodiments, a post-treatment clinical outcome is observable after about120 hours after administration. In some embodiments, a post-treatmentclinical outcome is observable after about 168 hours afteradministration. In some embodiments, a post-treatment clinical outcomeis observable after about 7 to about 10 days after administration. Insome embodiments, a post-treatment clinical outcome is observable afterabout 11 to about 20 days after administration. In some embodiments, apost-treatment clinical outcome is observable after about 21 to about 30days after administration.

In some embodiments, a method of preventing recurrence of bacterialvaginosis further comprises an alleviation of one or more symptoms ofbacterial vaginosis within up to about three days after administrationto the subject. In some embodiments, a method of preventing recurrenceof bacterial vaginosis further comprises an alleviation of one or moresymptoms of bacterial vaginosis within up to about three days afteradministration to the subject. In some embodiments, the one or moresymptoms include, but are not limited to, abnormal vaginal odor,abnormal vaginal discharge or a combination thereof. In someembodiments, alleviation refers to a lessening of the severity of one ormore symptoms. In some embodiments, alleviation of one or more symptomsof bacterial vaginosis occurs within about 24 hours afteradministration. In some embodiments, alleviation of one or more symptomsof bacterial vaginosis occurs within about 48 hours afteradministration. In some embodiments, alleviation of one or more symptomsof bacterial vaginosis occurs within about 72 hours after administrationto the subject. In some embodiments, alleviation of one or more symptomsof bacterial vaginosis occurs within about 96 hours after administrationto the subject. In some embodiments, alleviation of one or more symptomsof bacterial vaginosis occurs within about 120 hours afteradministration to the subject. In some embodiments, alleviation of oneor more symptoms of bacterial vaginosis occurs within about 168 hoursafter administration to the subject. In some embodiments, alleviation ofone or more symptoms of bacterial vaginosis occurs within about 7 toabout 10 days after administration to the subject. In some embodiments,alleviation of one or more symptoms of bacterial vaginosis occurs withinabout 11 to about 20 days after administration to the subject. In someembodiments, alleviation of one or more symptoms of bacterial vaginosisoccurs within about 21 to about 30 days after administration to thesubject.

In some embodiments, a method of preventing recurrence of bacterialvaginosis further comprises a resolution of one or more symptoms ofbacterial vaginosis within up to about seven days after administrationto the subject. In some embodiments, a method of preventing recurrenceof bacterial vaginosis further comprises a resolution of one or moresymptoms of bacterial vaginosis within up to about seven days afteradministration to the subject. In some embodiments, the one or moresymptoms include, but are not limited to, abnormal vaginal odor,abnormal vaginal discharge or a combination thereof. In someembodiments, resolution of one or more symptoms of bacterial vaginosisoccurs within about 24 hours after administration to the subject. Insome embodiments, resolution of one or more symptoms of bacterialvaginosis occurs within about 48 hours after administration. In someembodiments, resolution of one or more symptoms of bacterial vaginosisoccurs within about 72 hours after administration to the subject. Insome embodiments, resolution of one or more symptoms of bacterialvaginosis occurs within about 96 hours after administration to thesubject. In some embodiments, resolution of one or more symptoms ofbacterial vaginosis occurs within about 120 hours after administrationto the subject. In some embodiments, resolution of one or more symptomsof bacterial vaginosis occurs within about 168 hours afteradministration to the subject. In some embodiments, resolution of one ormore symptoms of bacterial vaginosis occurs within about 7 to about 10days after administration to the subject. In some embodiments,resolution of one or more symptoms of bacterial vaginosis occurs withinabout 11 to about 20 days after administration to the subject. In someembodiments, resolution of one or more symptoms of bacterial vaginosisoccurs within about 21 to about 30 days after administration to thesubject.

In some embodiments, a method of treating bacterial vaginosis in asubject in need thereof further comprises administering to at least oneof the subjects sexual partners, a therapeutically effective amount ofsecnidazole or pharmaceutically acceptable salts thereof. In someembodiments, a method of treating bacterial vaginosis in a subject inneed thereof further comprises administering to at least one of thesubjects sexual partners, a therapeutically effective amount ofsecnidazole or pharmaceutically acceptable salts thereof in amicrogranule formulation. In some embodiments, the secnidazolemicrogranule formulation may be suitable for oral administration. Insome embodiments, the secnidazole microgranule formulation comprises aplurality of microgranules. In some embodiments, the plurality ofmicrogranules are white to off-white in color. In some embodiments, theplurality of microgranules each have a particle size range of about 400micrometers to about 841 micrometers. In some embodiments, thesecnidazole microgranule formulation may be mixed, stirred, or otherwiseintegrated into a food substance. In some embodiments, the foodsubstance may be a semisolid or soft food. In some embodiments, the foodsubstance may include, but is not limited to applesauce, pudding, yogurtor the like. In some embodiments, integration of the secnidazolemicrogranule formulation into a food substance has a taste maskingfunction. In some embodiments, the at least one sexual partner of thesubject may be a male or a female. In some embodiments, a single dose ofa therapeutically effective amount of secnidazole or pharmaceuticallyacceptable salts thereof may be administered. In some embodiments, asingle dose of a therapeutically effective amount of secnidazole orpharmaceutically acceptable salts thereof in a microgranule formulationmay be administered. In some embodiments, multiple doses may be given atpre-determined intervals such as but not limited to once a week,bi-weekly, monthly, bimonthly for the duration of treatment. In someembodiment, the duration of treatment may be at least one week. In someembodiment, the duration of treatment may be at least one month. In someembodiments, the duration of treatment is about six months.

Some embodiments are directed to methods of treating vaginitis. In someembodiments, the vaginitis is trichomoniasis. Trichomoniasis is agenitourinary infection with the protozoan Trichomonas vaginalis. It isthe most common non-viral sexually transmitted disease (STD) worldwide.Women are affected more often than men. Trichomoniasis is one of thethree major causes of vaginal complaints among reproductive aged women,along with bacterial vaginosis and candida vulvovaginitis, and a causeof urethritis in men; however, the infection is often asymptomatic. Insome embodiments, a method of treating trichomoniasis in a subject inneed thereof comprises administering to the subject a therapeuticallyeffective amount of secnidazole or pharmaceutically acceptable saltsthereof in a microgranule formulation. In some embodiments, thesecnidazole microgranule formulation may be suitable for oraladministration. In some embodiments, the secnidazole microgranuleformulation comprises a plurality of microgranules. In some embodiments,the plurality of microgranules are white to off-white in color. In someembodiments, the plurality of microgranules each have a particle sizerange of about 400 micrometers to about 841 micrometers. In someembodiments, the secnidazole microgranule formulation may be mixed,stirred, or otherwise integrated into a food substance. In someembodiments, the food substance may be a semisolid or soft food. In someembodiments, the food substance may include, but is not limited toapplesauce, pudding, yogurt or the like. In some embodiments,integration of the secnidazole microgranule formulation into a foodsubstance has a taste masking function.

In some embodiments, the subject is a human. In yet other embodiments,the subject is a human female. In some embodiments, the human female isof an age ranging from a postmenarachal adolescent to a premenopausalwoman. In some embodiments, the subject is a pregnant human female.

In some embodiments, the subject is a female. In some embodiments, thesubject is an otherwise healthy female. In some embodiments, the subjectis a pregnant female. In some embodiments, the subject is an otherwisehealthy pregnant female. In some embodiments, the subject is a femalepresenting with purulent malodorous discharge (associated with burning,pruritus, dysuria, frequency, lower abdominal pain), dyspareunia,burning postcoital bleeding, dyspareunia, dysuria, a thin green-yellowfrothy discharge, vulvovaginal erythema (erythema of the vulva andvaginal mucosa), punctate hemorrhages, urethritis, cystitis, purulentvaginitis, sequamative inflammatory vaginitis, atrophic vaginitis,erosive lichen planus, an elevated vaginal pH (about 5.0 to about 6.0),and any combination thereof. In some embodiments, the subject isasymptomatic. In some embodiments, the subject is a female withconfirmed trichomoniasis. In some embodiments, the diagnosis ofTrichomonas vaginalis is confirmed by laboratory testing (including, butnot limited to motile trichomonads on wet mount, positive culture,increase in polymorphonuclear leukocytes, positive nucleic acidamplification test, or positive rapid antigen, nucleic acid probe testcervical cytology or any combination thereof). Microscopy (such as, butnot limited to culture on Diamond's medium) is a key step in theevaluation of vaginal discharge, and is often the first step in thediagnostic evaluation for trichomoniasis. Microscopy is convenient andlow cost. In some embodiments, nucleic acid amplification tests (NAAT)can then be done for subjects with non-diagnostic (or negative) wetmounts. In some embodiments, if NAAT is not available, rapid diagnostickits or culture are then performed. Additional laboratory tests includebut are not limited to the APTIMA Trichomonas vaginalis assay, theAPTIMA TV assay the Amplicor assay (PCR assay for detection of N.gonorrhoeae and C. trachomatis that has been modified to detect T.vaginalis in vaginal/endocervical swabs or urine); NuSwab VGor anycombination thereof positive rapid antigen, nucleic acid probe testinclude but are not limited to the Affirm VP III MicrobialIdentification System, and the OSOM Trichomonas Rapid Test. In someembodiments, the subject is a female with suspected trichomoniasis. Insome embodiments, suspected trichomoniasis is indicated by the presenceof purulent malodorous discharge (associated with burning, pruritus,dysuria, frequency, lower abdominal pain), or dyspareunia, burningpostcoital bleeding, dyspareunia, dysuria, a thin green-yellow frothydischarge, vulvovaginal erythema (erythema of the vulva and vaginalmucosa), punctate hemorrhages, urethritis, cystitis, purulent vaginitis,sequamative inflammatory vaginitis, atrophic vaginitis, erosive lichenplanus, elevated vaginal pH (about 5.0 to about 6.0), and anycombination thereof.

In some embodiments, a method of treating trichomoniasis in a subjectcomprises administering to the subject a single dose of atherapeutically effective amount of secnidazole in a microgranuleformulation, wherein the secnidazole comprises about 1 g to about 2 g ofthe microgranule formulation. In some embodiments, the secnidazolemicrogranule formulation is co-administered with an additional compoundselected from ethinyl estradiol (EE2), norethindrone (NET), or acombination thereof. In some embodiments, the secnidazole microgranuleformulation is mixed into a semisolid or soft food substance, such asbut not limited to applesauce, yogurt, and pudding. In some embodiments,the amount of the food substance is about 4-6 ounces.

In some embodiments, a method of treating trichomoniasis in a subjectcomprises administering to the subject a single dose of a secnidazolemicrogranule formulation that exhibits a maximum plasma concentration(C_(max)) of between about 34.5 μg/ml and about 58.3 μg/ml. In someembodiments, a method of treating bacterial vaginosis in a subjectcomprises administering to the subject a single dose of a secnidazolemicrogranule formulation that exhibits a maximum plasma concentration(C_(max)) of between about 17.4 μg/ml and about 26.5 μg/ml.

In some embodiments, a method of treating trichomoniasis in a subjectcomprises administering to the subject a single dose of a secnidazolemicrogranule formulation that exhibits a time to maximum plasmaconcentration (T_(max)) of about 3 hours to about 4.05 hours. In someembodiments, a method of treating trichomoniasis in a subject comprisesadministering to the subject a single dose of a secnidazole microgranuleformulation that exhibits a time to maximum plasma concentration(T_(max)) of about 2 hours to about 6 hours.

In some embodiments, a method of treating trichomoniasis in a subjectcomprises co-administering to the subject a single dose of atherapeutically effective amount of secnidazole in a microgranuleformulation and an additional compound selected from ethinyl estradiol(EE2), norethindrone (NET), or a combination thereof, wherein thesecnidazole comprises about 1 g to about 2 g of the microgranuleformulation. In some embodiments, the additional compound isco-administered on the same day as the secnidazole microgranuleformulation. In some embodiments, the additional compound isadministered on a different day than the secnidazole microgranuleformulation. In some embodiments, the secnidazole microgranuleformulation does not affect the contraceptive efficacy of the additionalcompound.

In some embodiments, a method of treating trichomoniasis in a subjectfurther comprises determining a post treatment clinical outcome. In someembodiments, a post treatment clinical outcome is indicative of aclinical outcome responder. In some embodiments, a clinical outcomeresponder is a subject that is asymptomatic. In some embodiments, aclinical outcome responder is a subject with normal vaginal discharge,normal vaginal pH, normal laboratory testing results (including, but notlimited to the absence of motile trichomonads on wet mount, negativeculture, normal polymorphonuclear leukocytes, negative nucleic acidamplification test, negative rapid antigen, negative nucleic acid probetest, negative rapid diagnostic kits or culture, negative cervicalcytology, or any combination thereof) after treatment with an oralmicrogranule formulation comprising about 1 to about 2 grams ofsecnidazole. In some embodiments, a clinical outcome responder is asubject with without purulent malodorous discharge (associated withburning, pruritus, dysuria, frequency, lower abdominal pain), ordyspareunia, burning postcoital bleeding, dyspareunia, dysuria, a thingreen-yellow frothy discharge, vulvovaginal erythema (erythema of thevulva and vaginal mucosa), punctate hemorrhages, urethritis, cystitis,purulent vaginitis, sequamative inflammatory vaginitis, atrophicvaginitis, erosive lichen planus, elevated vaginal pH (about 5.0 toabout 6.0), and any combination thereof. In some embodiments, apost-treatment clinical outcome is observable after about 24 hours afteradministration. In some embodiments, a post-treatment clinical outcomeis observable after about 48 hours after administration. In someembodiments, a post-treatment clinical outcome is observable after about72 hours after administration. In some embodiments, a post-treatmentclinical outcome is observable after about 96 hours afteradministration. In some embodiments, a post-treatment clinical outcomeis observable after about 120 hours after administration. In someembodiments, a post-treatment clinical outcome is observable after about168 hours after administration. In some embodiments, a post-treatmentclinical outcome is observable after about 7 to about 10 days afteradministration. In some embodiments, a post-treatment clinical outcomeis observable after about 11 to about 20 days after administration. Insome embodiments, a post-treatment clinical outcome is observable afterabout 21 to about 30 days after administration.

In some embodiments, a method of treating trichomoniasis furthercomprises an alleviation of one or more symptoms of trichomoniasiswithin up to about three days after administration to the subject. Insome embodiments, a method of treating trichomoniasis further comprisesan alleviation of one or more symptoms of trichomoniasis within up toabout three days after administration to the subject. In someembodiments, the one or more symptoms include, but are not limited to,purulent malodorous discharge (associated with burning, pruritus,dysuria, frequency, lower abdominal pain), or dyspareunia, burningpostcoital bleeding, dyspareunia, dysuria, a thin green-yellow frothydischarge, vulvovaginal erythema (erythema of the vulva and vaginalmucosa), punctate hemorrhages, urethritis, cystitis, purulent vaginitis,sequamative inflammatory vaginitis, atrophic vaginitis, erosive lichenplanus, elevated vaginal pH (about 5.0 to about 6.0), and anycombination thereof. In some embodiments, alleviation refers to alessening of the severity of one or more symptoms. In some embodiments,alleviation of one or more symptoms of trichomoniasis occurs withinabout 24 hours after administration. In some embodiments, alleviation ofone or more symptoms of trichomoniasis occurs within about 48 hoursafter administration. In some embodiments, alleviation of one or moresymptoms of trichomoniasis occurs within about 72 hours afteradministration to the subject. In some embodiments, alleviation of oneor more symptoms of trichomoniasis occurs within about 96 hours afteradministration to the subject. In some embodiments, alleviation of oneor more symptoms of trichomoniasis occurs within about 120 hours afteradministration to the subject. In some embodiments, alleviation of oneor more symptoms of trichomoniasis occurs within about 168 hours afteradministration to the subject. In some embodiments, alleviation of oneor more symptoms of trichomoniasis occurs within about 7 to about 10days after administration to the subject. In some embodiments,alleviation of one or more symptoms of trichomoniasis occurs withinabout 11 to about 20 days after administration to the subject. In someembodiments, alleviation of one or more symptoms of trichomoniasisoccurs within about 21 to about 30 days after administration to thesubject.

In some embodiments, a method of treating trichomoniasis furthercomprises a resolution of one or more symptoms of trichomoniasis withinup to about seven days after administration to the subject. In someembodiments, a method of treating trichomoniasis further comprises aresolution of one or more symptoms of trichomoniasis within up to aboutseven days after administration to the subject. In some embodiments, theone or more symptoms include, but are not limited to, purulentmalodorous discharge (associated with burning, pruritus, dysuria,frequency, lower abdominal pain), or dyspareunia, burning postcoitalbleeding, dyspareunia, dysuria, a thin green-yellow frothy discharge,vulvovaginal erythema (erythema of the vulva and vaginal mucosa),punctate hemorrhages, urethritis, cystitis, purulent vaginitis,sequamative inflammatory vaginitis, atrophic vaginitis, erosive lichenplanus, elevated vaginal pH (about 5.0 to about 6.0), and anycombination thereof. In some embodiments, resolution of one or moresymptoms of trichomoniasis occurs within about 24 hours afteradministration to the subject. In some embodiments, resolution of one ormore symptoms of trichomoniasis occurs within about 48 hours afteradministration. In some embodiments, resolution of one or more symptomsof trichomoniasis occurs within about 72 hours after administration tothe subject. In some embodiments, resolution of one or more symptoms oftrichomoniasis occurs within about 96 hours after administration to thesubject. In some embodiments, resolution of one or more symptoms oftrichomoniasis occurs within about 120 hours after administration to thesubject. In some embodiments, resolution of one or more symptoms oftrichomoniasis occurs within about 168 hours after administration to thesubject. In some embodiments, resolution of one or more symptoms oftrichomoniasis occurs within about 7 to about 10 days afteradministration to the subject. In some embodiments, resolution of one ormore symptoms of trichomoniasis occurs within about 11 to about 20 daysafter administration to the subject. In some embodiments, resolution ofone or more symptoms of trichomoniasis occurs within about 21 to about30 days after administration to the subject.

In some embodiments, treatment of trichomoniasis with a single, 2 gramdose of secnidazole in a microgranule formulation results in better thanexpected efficacy compared with FDA approved drugs used in the treatmentof trichomoniasis. In some embodiments, a single dose of 2 grams ofsecnidazole results in a better than expected efficacy compared with FDAapproved drugs currently used in the treatment of trichomoniasis. Insome embodiments, treatment of trichomoniasis with a single, 2 gram doseof secnidazole results in superior efficacy compared with FDA approveddrugs used in the treatment of trichomoniasis. In some embodiments, asingle dose of 2 grams of secnidazole results in superior efficacycompared with FDA drugs used in the treatment of trichomoniasisrequiring a single dose during treatment.

In some embodiments, treatment of trichomoniasis with a single, 2 gramdose of secnidazole results in a better than expected safety profilecompared with FDA approved drugs used in the treatment oftrichomoniasis. In some embodiments, a single dose of 2 grams ofsecnidazole results in a better than expected safety profile comparedwith FDA approved drugs used in the treatment of trichomoniasisrequiring multiple doses during treatment. In some embodiments,treatment of trichomoniasis with a single, 2 gram dose of secnidazoleresults in a superior safety profile compared with FDA approved drugsused in the treatment of trichomoniasis. In some embodiments, a singledose of 2 grams of secnidazole results in a superior safety profilecompared with FDA approved drugs used in the treatment of trichomoniasisrequiring a single dose during treatment.

In some embodiments, a method of treating trichomoniasis in a subject inneed thereof further comprises administering to at least one of thesubjects sexual partners, a therapeutically effective amount ofsecnidazole or pharmaceutically acceptable salts thereof in amicrogranule formulation. In some embodiments, the secnidazolemicrogranule formulation may be suitable for oral administration. Insome embodiments, the secnidazole microgranule formulation comprises aplurality of microgranules. In some embodiments, the plurality ofmicrogranules are white to off-white in color. In some embodiments, theplurality of microgranules each have a particle size range of about 400micrometers to about 841 micrometers. In some embodiments, thesecnidazole microgranule formulation may be mixed, stirred, or otherwiseintegrated into a food substance. In some embodiments, the foodsubstance may be a semisolid or soft food. In some embodiments, the foodsubstance may include, but is not limited to applesauce, pudding, yogurtor the like. In some embodiments, integration of the secnidazolemicrogranule formulation into a food substance has a taste maskingfunction.

In some embodiments, the subject is a human. In yet other embodiments,the subject is a human female. In some embodiments, the human female isof an age ranging from a postmenarachal adolescent to a premenopausalwoman. In some embodiments, the subject is a pregnant human female. Insome embodiments, the at least one sexual partner of the subject may bea male or a female.

In some embodiments, a method of treating bacterial vaginosis and/ortrichmoniasis in a subject in need thereof comprises administering tothe subject a therapeutically effective amount of secnidazole orpharmaceutically acceptable salts thereof in a microgranule formulation.In some embodiments, the secnidazole microgranule formulation may besuitable for oral administration. In some embodiments, the secnidazolemicrogranule formulation comprises a plurality of microgranules. In someembodiments, the plurality of microgranules are white to off-white incolor. In some embodiments, the plurality of microgranules each have aparticle size range of about 400 micrometers to about 841 micrometers.In some embodiments, the secnidazole microgranule formulation may bemixed, stirred, or otherwise integrated into a food substance. In someembodiments, the food substance may be a semisolid or soft food. In someembodiments, the food substance may include, but is not limited toapplesauce, pudding, yogurt or the like. In some embodiments,integration of the secnidazole microgranule formulation into a foodsubstance has a taste masking function.

In some embodiments, the subject is a human. In yet other embodiments,the subject is a human female. In some embodiments, the human female isof an age ranging from a postmenarachal adolescent to a premenopausalwoman. In some embodiments, the subject is a pregnant human female.

In some embodiments, the subject is a female. In some embodiments, thesubject is an otherwise healthy female. In some embodiments, the subjectis a pregnant female. In some embodiments, the subject is an otherwisehealthy pregnant female. In some embodiments, the subject is a femalehaving had 3 or fewer bacterial vaginosis infections in the past 12months. In some embodiments, the subject is a female having had 4 ormore bacterial vaginosis infections in the past twelve months. In someembodiments, the subject is a female with recurring bacterial vaginosis.In some embodiments, a subject with recurring bacterial vaginosis is asubject with 4 or more bacterial vaginosis infections within atwelve-month period. In some embodiments, the subject is a female withfrequent bacterial vaginosis infections. In some embodiments, a femalewith frequent bacterial vaginosis infections is a female with 4 or morebacterial vaginosis infections within a twelve-month period. In someembodiments, the subject is a female presenting with an off-white (milkyor gray), thin, homogeneous vaginal discharge, vaginal pH greater thanor equal to 4.7, presence of clue cells of greater than or equal to 20%of the total epithelial cells on microscopic examination of a vaginalsaline wet mount, a positive 10% KOH Whiff test or a combinationthereof. In some embodiments, the subject is a female presenting with anoff-white (milky or gray), thin, homogeneous vaginal discharge, vaginalpH greater than or equal to 4.7, the presence of clue cells of greaterthan or equal to 20% of the total epithelial cells on microscopicexamination of a vaginal saline wet mount, and a positive 10% KOH Whifftest. In some embodiments, the subject is a female with confirmedbacterial vaginosis. In some embodiments, bacterial vaginosis isconfirmed by the presence of four (4) Amsel criteria parameters selectedfrom an off-white (milky or gray), thin, homogeneous vaginal discharge,vaginal pH greater than or equal to 4.7, the presence of clue cells ofgreater than or equal to 20% of the total epithelial cells onmicroscopic examination of a vaginal saline wet mount, a positive 10%KOH Whiff test and a gram stain slide Nugent score equal to, or higherthan four (4) on bacterial analysis of vaginal samples. In someembodiments, the subject is a female with suspected bacterial vaginosis.In some embodiments, suspected bacterial vaginosis is indicated by thepresence of four (4) Amsel criteria parameters selected from anoff-white (milky or gray), thin, homogeneous vaginal discharge, vaginalpH greater than or equal to 4.7, the presence of clue cells of greaterthan or equal to 20% of the total epithelial cells on microscopicexamination of a vaginal saline wet mount, and a positive 10% KOH Whifftest. In some embodiments, the subject is a female presenting with anoff-white (milky or gray), thin, homogeneous vaginal discharge, odor, ora combination thereof. In some embodiments, the subject is a femalepresenting with purulent malodorous discharge (associated with burning,pruritus, dysuria, frequency, lower abdominal pain), dyspareunia,burning postcoital bleeding, dyspareunia, dysuria, a thin green-yellowfrothy discharge, vulvovaginal erythema (erythema of the vulva andvaginal mucosa), punctate hemorrhages, urethritis, cystitis, purulentvaginitis, sequamative inflammatory vaginitis, atrophic vaginitis,erosive lichen planus, an elevated vaginal pH (about 5.0 to about 6.0),and any combination thereof. In some embodiments, the subject isasymptomatic. In some embodiments, the subject is a female withconfirmed trichomoniasis. In some embodiments, the diagnosis ofTrichomonas vaginalis is confirmed by laboratory testing (including, butnot limited to motile trichomonads on wet mount, positive culture,increase in polymorphonuclear leukocytes, positive nucleic acidamplification test, or positive rapid antigen, nucleic acid probe testcervical cytology or any combination thereof). Microscopy (such as, butnot limited to culture on Diamond's medium) is a key step in theevaluation of vaginal discharge, and is often the first step in thediagnostic evaluation for trichomoniasis. Microscopy is convenient andlow cost. In some embodiments, nucleic acid amplification tests (NAAT)can then be done for subjects with non-diagnostic (or negative) wetmounts. In some embodiments, if NAAT is not available, rapid diagnostickits or culture are then performed. Additional laboratory tests includebut are not limited to the APTIMA Trichomonas vaginalis assay, theAPTIMA TV assay the Amplicor assay (PCR assay for detection of N.gonorrhoeae and C. trachomatis that has been modified to detect T.vaginalis in vaginal/endocervical swabs or urine); NuSwab VGor anycombination thereof positive rapid antigen, nucleic acid probe testinclude but are not limited to the Affirm VP III MicrobialIdentification System, and the OSOM Trichomonas Rapid Test. In someembodiments, the subject is a female with suspected trichomoniasis. Insome embodiments, suspected trichomoniasis is indicated by presence ofpurulent malodorous discharge (associated with burning, pruritus,dysuria, frequency, lower abdominal pain), or dyspareunia, burningpostcoital bleeding, dyspareunia, dysuria, a thin green-yellow frothydischarge, vulvovaginal erythema (erythema of the vulva and vaginalmucosa), punctate hemorrhages, urethritis, cystitis, purulent vaginitis,sequamative inflammatory vaginitis, atrophic vaginitis, erosive lichenplanus, elevated vaginal pH (about 5.0 to about 6.0), and anycombination thereof. In some embodiments, the subject is suspected ofhaving both bacterial vaginosis and/or trichmoniasis. In someembodiments, a diagnosis of bacterial vaginosis and/or trichmoniasis isnot confirmed.

In some embodiments, a method of treating bacterial vaginosis and/ortrichmoniasis in a subject comprises administering to the subject asingle dose of a therapeutically effective amount of secnidazole in amicrogranule formulation, wherein the secnidazole comprises about 1 g toabout 2 g of the microgranule formulation. In some embodiments, thesecnidazole microgranule formulation is mixed into a semisolid or softfood substance, such as but not limited to applesauce yogurt andpudding. In some embodiments, the amount of the food substance is about4-6 ounces.

In some embodiments, a method of treating bacterial vaginosis and/ortrichmoniasis in a subject comprises administering to the subject asingle dose of a secnidazole microgranule formulation that exhibits amaximum plasma concentration (C_(max)) of between about 34.5 μg/ml andabout 58.3 μg/ml. In some embodiments, a method of treating bacterialvaginosis in a subject comprises administering to the subject a singledose of a secnidazole microgranule formulation that exhibits a maximumplasma concentration (C_(max)) of between about 17.4 μg/ml and about26.5 μg/ml.

In some embodiments, a method of treating bacterial vaginosis and/ortrichmoniasis in a subject comprises administering to the subject asingle dose of a secnidazole microgranule formulation that exhibits atime to maximum plasma concentration (T_(max)) of about 3 hours to about4.05 hours. In some embodiments, a method of treating bacterialvaginosis in a subject comprises administering to the subject a singledose of a secnidazole microgranule formulation that exhibits a time tomaximum plasma concentration (T_(max)) of about 2 hours to about 6hours.

In some embodiments, a method of treating bacterial vaginosis and/ortrichmoniasis in a subject comprises co-administering to the subject asingle dose of a therapeutically effective amount of secnidazole in amicrogranule formulation and an additional compound selected fromethinyl estradiol (EE2), norethindrone (NET), or a combination thereof,wherein the secnidazole comprises about 1 g to about 2 g of themicrogranule formulation. In some embodiments, the additional compoundis co-administered on the same day as the secnidazole microgranuleformulation. In some embodiments, the additional compound isadministered on a different day than the secnidazole microgranuleformulation. In some embodiments, the secnidazole microgranuleformulation does not affect the contraceptive efficacy of the additionalcompound.

In some embodiments, a method of treating bacterial vaginosis and/ortrichmoniasis in a subject further comprises determining a posttreatment clinical outcome. In some embodiments, a post treatmentclinical outcome is indicative of a clinical outcome responder. Someembodiments further comprise determining a post-treatment clinicaloutcome. In some embodiments, a post-treatment clinical outcome ofclinical cure is defined as a clinical outcome responder. In someembodiments, a clinical outcome responder is a subject with normalvaginal discharge, a negative KOH Whiff test, and clue cells less thanor equal to 20% of the total epithelial cells on microscopic examinationof a vaginal saline wet mount after treatment with a microgranuleformulation comprising about 1 to about 2 grams of secnidazole. In someembodiments, a clinical outcome responder has a gram stain slide Nugentscore of less than four (4) after treatment with a single dose ofsecnidazole. In yet other embodiments, a clinical outcome responder is asubject with normal vaginal discharge, a negative KOH Whiff test, cluecells less than 20% of total epithelial cells, and a gram stain slideNugent score of less than four (4) after treatment with a single dose ofsecnidazole. In some embodiments, a clinical outcome responder has agram stain slide Nugent score of less than four (4) after treatment witha 2 gram single dose of secnidazole. In yet other embodiments, aclinical outcome responder is a subject with normal vaginal discharge, anegative KOH Whiff test, clue cells less than 20% of total epithelialcells, and a gram stain slide Nugent score of less than four (4) aftertreatment with a 2 gram single dose of secnidazole. In some embodiments,a post-treatment clinical outcome is observable after about 24 hoursafter administration. In some embodiments, a post-treatment clinicaloutcome is observable after about 48 hours after administration. In someembodiments, a post-treatment clinical outcome is observable after about72 hours after administration. In some embodiments, a post-treatmentclinical outcome is observable after about 96 hours afteradministration. In some embodiments, a post-treatment clinical outcomeis observable after about 120 hours after administration. In someembodiments, a post-treatment clinical outcome is observable after about168 hours after administration. In some embodiments, a post-treatmentclinical outcome is observable after about 7 to about 10 days afteradministration. In some embodiments, a post-treatment clinical outcomeis observable after about 11 to about 20 days after administration. Insome embodiments, a post-treatment clinical outcome is observable afterabout 21 to about 30 days after administration. In some embodiments, amethod of treating trichomoniasis in a subject further comprisesdetermining a post treatment clinical outcome. In some embodiments, apost treatment clinical outcome is indicative of a clinical outcomeresponder. In some embodiments, a clinical outcome responder is asubject that is asymptomatic. In some embodiments, a clinical outcomeresponder is a subject with normal vaginal discharge, normal vaginal pH,normal laboratory testing results (including, but not limited to theabsence of motile trichomonads on wet mount, negative culture, normalpolymorphonuclear leukocytes, negative nucleic acid amplification test,negative rapid antigen, negative nucleic acid probe test, negative rapiddiagnostic kits or culture, negative cervical cytology, or anycombination thereof) after treatment with an oral microgranuleformulation comprising about 1 to about 2 grams of secnidazole. In someembodiments, a clinical outcome responder is a subject with withoutpurulent malodorous discharge (associated with burning, pruritus,dysuria, frequency, lower abdominal pain), or dyspareunia, burningpostcoital bleeding, dyspareunia, dysuria, a thin green-yellow frothydischarge, vulvovaginal erythema (erythema of the vulva and vaginalmucosa), punctate hemorrhages, urethritis, cystitis, purulent vaginitis,sequamative inflammatory vaginitis, atrophic vaginitis, erosive lichenplanus, elevated vaginal pH (about 5.0 to about 6.0), and anycombination thereof. In some embodiments, a post-treatment clinicaloutcome is observable after about 24 hours after administration. In someembodiments, a post-treatment clinical outcome is observable after about48 hours after administration. In some embodiments, a post-treatmentclinical outcome is observable after about 72 hours afteradministration. In some embodiments, a post-treatment clinical outcomeis observable after about 96 hours after administration. In someembodiments, a post-treatment clinical outcome is observable after about120 hours after administration. In some embodiments, a post-treatmentclinical outcome is observable after about 168 hours afteradministration. In some embodiments, a post-treatment clinical outcomeis observable after about 7 to about 10 days after administration. Insome embodiments, a post-treatment clinical outcome is observable afterabout 11 to about 20 days after administration. In some embodiments, apost-treatment clinical outcome is observable after about 21 to about 30days after administration.

In some embodiments, a method of treating bacterial vaginosis and/ortrichmoniasis further comprises an alleviation of one or more symptomsof bacterial vaginosis within up to about three days afteradministration to the subject. In some embodiments, a method of treatingbacterial vaginosis further comprises an alleviation of one or moresymptoms of bacterial vaginosis within up to about three days afteradministration to the subject. In some embodiments, the one or moresymptoms include, but are not limited to, abnormal vaginal odor,abnormal vaginal discharge or a combination thereof. In someembodiments, alleviation refers to a lessening of the severity of one ormore symptoms. In some embodiments, alleviation of one or more symptomsof bacterial vaginosis occurs within about 24 hours afteradministration. In some embodiments, alleviation of one or more symptomsof bacterial vaginosis occurs within about 48 hours afteradministration. In some embodiments, alleviation of one or more symptomsof bacterial vaginosis occurs within about 72 hours after administrationto the subject. In some embodiments, alleviation of one or more symptomsof bacterial vaginosis occurs within about 96 hours after administrationto the subject. In some embodiments, alleviation of one or more symptomsof bacterial vaginosis occurs within about 120 hours afteradministration to the subject. In some embodiments, alleviation of oneor more symptoms of bacterial vaginosis occurs within about 168 hoursafter administration to the subject. In some embodiments, alleviation ofone or more symptoms of bacterial vaginosis occurs within about 7 toabout 10 days after administration to the subject. In some embodiments,alleviation of one or more symptoms of bacterial vaginosis occurs withinabout 11 to about 20 days after administration to the subject. In someembodiments, alleviation of one or more symptoms of bacterial vaginosisoccurs within about 21 to about 30 days after administration to thesubject. In some embodiments, a method of treating trichomoniasis in asubject further comprises determining a post treatment clinical outcome.In some embodiments, a post treatment clinical outcome is indicative ofa clinical outcome responder. In some embodiments, a clinical outcomeresponder is a subject that is asymptomatic. In some embodiments, aclinical outcome responder is a subject with normal vaginal discharge,normal vaginal pH, normal laboratory testing results (including, but notlimited to the absence of motile trichomonads on wet mount, negativeculture, normal polymorphonuclear leukocytes, negative nucleic acidamplification test, negative rapid antigen, negative nucleic acid probetest, negative rapid diagnostic kits or culture, negative cervicalcytology, or any combination thereof) after treatment with an oralmicrogranule formulation comprising about 1 to about 2 grams ofsecnidazole. In some embodiments, a clinical outcome responder is asubject with without purulent malodorous discharge (associated withburning, pruritus, dysuria, frequency, lower abdominal pain), ordyspareunia, burning postcoital bleeding, dyspareunia, dysuria, a thingreen-yellow frothy discharge, vulvovaginal erythema (erythema of thevulva and vaginal mucosa), punctate hemorrhages, urethritis, cystitis,purulent vaginitis, sequamative inflammatory vaginitis, atrophicvaginitis, erosive lichen planus, elevated vaginal pH (about 5.0 toabout 6.0), and any combination thereof. In some embodiments, apost-treatment clinical outcome is observable after about 24 hours afteradministration. In some embodiments, a post-treatment clinical outcomeis observable after about 48 hours after administration. In someembodiments, a post-treatment clinical outcome is observable after about72 hours after administration. In some embodiments, a post-treatmentclinical outcome is observable after about 96 hours afteradministration. In some embodiments, a post-treatment clinical outcomeis observable after about 120 hours after administration. In someembodiments, a post-treatment clinical outcome is observable after about168 hours after administration. In some embodiments, a post-treatmentclinical outcome is observable after about 7 to about 10 days afteradministration. In some embodiments, a post-treatment clinical outcomeis observable after about 11 to about 20 days after administration. Insome embodiments, a post-treatment clinical outcome is observable afterabout 21 to about 30 days after administration.

In some embodiments, a method of treating bacterial vaginosis and/ortrichmoniasis further comprises a resolution of one or more symptoms ofbacterial vaginosis within up to about seven days after administrationto the subject. In some embodiments, a method of treating bacterialvaginosis further comprises a resolution of one or more symptoms ofbacterial vaginosis within up to about seven days after administrationto the subject. In some embodiments, the one or more symptoms include,but are not limited to, abnormal vaginal odor, abnormal vaginaldischarge or a combination thereof. In some embodiments, resolution ofone or more symptoms of bacterial vaginosis occurs within about 24 hoursafter administration to the subject. In some embodiments, resolution ofone or more symptoms of bacterial vaginosis occurs within about 48 hoursafter administration. In some embodiments, resolution of one or moresymptoms of bacterial vaginosis occurs within about 72 hours afteradministration to the subject. In some embodiments, resolution of one ormore symptoms of bacterial vaginosis occurs within about 96 hours afteradministration to the subject. In some embodiments, resolution of one ormore symptoms of bacterial vaginosis occurs within about 120 hours afteradministration to the subject. In some embodiments, resolution of one ormore symptoms of bacterial vaginosis occurs within about 168 hours afteradministration to the subject. In some embodiments, resolution of one ormore symptoms of bacterial vaginosis occurs within about 7 to about 10days after administration to the subject. In some embodiments,resolution of one or more symptoms of bacterial vaginosis occurs withinabout 11 to about 20 days after administration to the subject. In someembodiments, resolution of one or more symptoms of bacterial vaginosisoccurs within about 21 to about 30 days after administration to thesubject. In some embodiments, a method of treating trichomoniasisfurther comprises a resolution of one or more symptoms of trichomoniasiswithin up to about seven days after administration to the subject. Insome embodiments, a method of treating trichomoniasis further comprisesa resolution of one or more symptoms of trichomoniasis within up toabout seven days after administration to the subject. In someembodiments, the one or more symptoms include, but are not limited to,purulent malodorous discharge (associated with burning, pruritus,dysuria, frequency, lower abdominal pain), or dyspareunia, burningpostcoital bleeding, dyspareunia, dysuria, a thin green-yellow frothydischarge, vulvovaginal erythema (erythema of the vulva and vaginalmucosa), punctate hemorrhages, urethritis, cystitis, purulent vaginitis,sequamative inflammatory vaginitis, atrophic vaginitis, erosive lichenplanus, elevated vaginal pH (about 5.0 to about 6.0), and anycombination thereof. In some embodiments, resolution of one or moresymptoms of trichomoniasis occurs within about 24 hours afteradministration to the subject. In some embodiments, resolution of one ormore symptoms of trichomoniasis occurs within about 48 hours afteradministration. In some embodiments, resolution of one or more symptomsof trichomoniasis occurs within about 72 hours after administration tothe subject. In some embodiments, resolution of one or more symptoms oftrichomoniasis occurs within about 96 hours after administration to thesubject. In some embodiments, resolution of one or more symptoms oftrichomoniasis occurs within about 120 hours after administration to thesubject. In some embodiments, resolution of one or more symptoms oftrichomoniasis occurs within about 168 hours after administration to thesubject. In some embodiments, resolution of one or more symptoms oftrichomoniasis occurs within about 7 to about 10 days afteradministration to the subject. In some embodiments, resolution of one ormore symptoms of trichomoniasis occurs within about 11 to about 20 daysafter administration to the subject. In some embodiments, resolution ofone or more symptoms of trichomoniasis occurs within about 21 to about30 days after administration to the subject.

This invention and embodiments illustrating the method and materialsused may be further understood by reference to the followingnon-limiting examples.

EXAMPLES Example 1

This study evaluated the safety and pharmacokinetics (PK) of a 1 g or 2g dose of a new microgranule formulation (formulation shown in Table 2)for SYM-1219, which contains a 5-nitroimidazole derivative(secnidazole), being developed for the treatment of women with bacterialvaginosis (BV).

TABLE 2 Composition of SYM-1219 Drug Product Quantity, Quantity, Qualitymg/1 g mg/2 g Component Function Standard Dose Dose Secnidazole ActiveManufacturer's 1000.00 2000.00 Ingredient specifications Sugar SpheresInert core NF 940.00 1880.00 (size 35-40 mesh) Povidone Dispersion USP100.82 201.63 (Plasdone K- and 29/32) binding Polyethylene Seal coatingNF 41.50 83.00 Glycol 4000 Eudragit NE30D Modified NF 138.30 273.60(Ethyl release Acrylate[[,]] coating Methyl Methacrylate Copolymer TalcAnti-tacking USP 138.30 273.60 agent Total 2365.00 4730.00

Methods: 28 healthy female subjects (14/group) ages 18-65 years wererandomized to receive a single oral dose of either 1 or 2 grams ofSYM-1219, mixed into 4 oz. of applesauce. Serial blood samples werecollected over 168 hours to determine SYM-1219 plasma concentrations. Anon-compartmental analysis was performed and the PK parameters for eachtreatment group are reported. Safety was evaluated by recording adverseevents, vital signs, ECGs and laboratory tests.

Results: All subjects (N=28) completed the study and were evaluable forPK and safety. Table 2 below discloses the plasma pharmacokinetics ofSYM-1219 (1 g or 2 g) administered according to methods described inthis Example to fasted healthy female subjects. Table 4 below disclosesthe urine pharmacokinetics of SYM-1219 (1 g or 2 g) administeredaccording to methods described in this Example to fasted healthy femalesubjects. FIG. 1 illustrates the mean (+SD) SYM-1219 plasmaconcentration (ug/mL) for the 1 g dose (circle markers) and the 2 g dose(triangle markers) over time.

The PK of SYM-1219 was consistent between individuals, as demonstratedby low coefficients of variation (% CV) estimates. Mean maximumconcentrations were 22.6 mcg/mL for the 1 g dose and 45.4 mcg/mL for the2 g dose and were achieved by approximately 4 hrs. in both dose groups.Exposure estimates (AUCinf) were 619 mcg*hr./mL for the 1 g dose and1331 mcg*hr./mL for the 2 g dose. The pharmacokinetics of SYM-1219 wasdose proportional when comparing the 1 and 2 g doses. The intersubjectvariability was low (<20% CV) for C_(max) and AUC. Urinary excretion ofunchanged SYM-1219 accounted for 13.6% (1 g dose) and 15.3% (2 g dose)of the administered dose. The amount excreted into the urine increasedin proportion to dose. Renal clearance was similar after 1 g and 2 gdoses and the renal clearance is only a small percentage (ie, <5%) ofthe glomerular filtration rate typically found in healthy subjects withnormal renal function.

SYM-1219 was safe and well-tolerated. The most common adverse eventswere headache and nausea. All adverse events were mild and resolvedwithout sequelae. There were no significant changes in vital signs,electrocardiogram (ECG) or laboratory parameters.

TABLE 3 Plasma Pharmacokinetics of SYM-1219 After a Single Oral DoseAdministered to Fasted Healthy Female Subjects (Part A) PharmacokineticPopulation SYM-1219 1 gram SYM-1219 2 grams Parameter (N = 14) (N = 14)C_(max) (μg/mL) n 14   14 Mean (SD) 22.62 (2.871) 45.43 (7.642) % CV12.69   16.82 Geometric Mean (SD) 22.45 (2.938) 44.84 (7.467) Median22.75   45.05 Min, Max 17.4, 26.5 34.5, 58.3 T_(max) (h) n 14   14Median   3.060    4.000 Min, Max 2.00, 6.00 3.00, 4.05 AUC_(0-t)(h*μg/mL) n 14   14 Mean (SD) 609.66 (96.685) 1322.40 (230.256) % CV15.86   17.41 Geometric Mean (SD) 602.94 (92.067) 1305.35 (214.383)Median 587.42   1290.41 Min, Max 487.6, 832.5 1048.5, 1899.5 AUC_(0-∞)(h*μg/mL) n 14   14 Mean (SD) 618.89 (98.093) 1331.63 (230.159) % CV15.85   17.28 Geometric Mean (SD) 612.09 (93.248) 1314.74 (214.081)Median 595.25   1299.10 Min, Max 498.5, 847.0 1055.1, 1911.9 t_(1/2) (h)n 14   14 Mean (SD) 17.05 (1.611) 16.86 (2.649) Median 16.79   17.13Min, Max 14.7, 20.4 11.3, 20.4 λz (1/h) n 14   14 Mean (SD)  0.04099(0.003757)  0.04220 (0.007544) Median   0.04129     0.04047 Min, Max0.0339, 0.0471 0.0340, 0.0613 Source: Table 14.1.2.4, Listing16.2.1.11.2

TABLE 4 Urine Pharmacokinetics of SYM-1219 After a Single Oral DoseAdministered to Fasted Healthy Female Subjects (Part A) PharmacokineticPopulation SYM-1219 1 gram SYM-1219 2 grams Parameter (N = 14) (N = 14)Ae₀₋₁₆₈ (g) n 14    14    Mean (SD) 0.136 (0.0238) 0.306 (0.0711) % CV17.478 23.234 Geometric Mean (SD) 0.134 (0.0241) 0.300 (0.0602) Median 0.140  0.299 Min, Max 0.10, 0.18 0.22, 0.52 CLr (mL/min) n 14    14   Mean (SD) 3.742 (0.8255) 3.935 (1.0568) % CV 22.060 26.859 GeometricMean (SD) 3.650 (0.8701) 3.801 (1.0532) Median  3.965  3.962 Min, Max2.37, 4.89 2.23, 6.19 % FE n 14    14    Mean (SD) 13.602 (2.3773) 15.300 (3.5549)  % CV 17.478 23.234 Geometric Mean (SD) 13.403 (2.4100) 14.991 (3.0081)  Median 13.981 14.943 Min, Max 10.19, 17.56 11.03, 26.20Source: Table 14.1.2.5, Listing 16.2.1.12.1

Conclusions: This study characterized the single dose PK of a 1 g and 2g dose of a new microgranule formulation of a 5-nitroimidazolederivative (secnidazole), SYM-1219. SYM-1219 was safe andwell-tolerated. The consistent PK and resulting exposure, with lowvariability between subjects, makes this a promising new therapeuticoption. Ongoing studies will further evaluate the safety and efficacy ofSYM-1219 for the treatment of women with BV.

Example 2

Background: This study evaluated the effect of a single 2 g dose ofSYM-1219, a new microgranule formulation containing a 5-nitroimidazolederivative (secnidazole) in development to treat women with bacterialvaginosis, on the pharmacokinetics (PK) of ethinyl estradiol (EE2) andnorethindrone (NET).

Methods: Fifty-four (54) healthy female subjects, ages 18-65, receivedEE2/NET alone and in combination, where SYM-1219+ EE2/NET wereco-administered on Day 1 (Group B1; N=27) or SYM-1219 on Day 1 andEE2/NET on Day 2 (Group B2; N=27). Serial blood samples were drawn tomeasure plasma concentrations of EE2/NET. A non-compartmental analysiswas performed and the PK parameters for each treatment group arereported. Safety was evaluated by recording of adverse events, vitalsigns, ECGs and standard laboratory tests.

Results: Fifty-one (N=26 for B1 and N=25 for B2) subjects completed thestudy. FIG. 2 illustrates the mean (+SD) EE2 plasma concentrations(pg/mL) over time when EE2 was administered alone (circle markers) onDay 1 of Period 1 and when EE2 was administered in conjunction with 2gram microgranule formulation SYM-1219 on Day 1 of Period 2 (trianglemarkers) (Group B1). FIG. 3 illustrates the mean (+SD) EE2 plasmaconcentrations (pg/mL) over time when (1) EE2 was administered alone(circle markers) on Day 1 of Period 1; and (2) when 2 gram microgranuleformulation SYM-1219 was administered on Day 1 of Period 2 and EE2 wasadministered on Day 2 of Period 2 (triangle markers) (Group B2). FIG. 4illustrates the mean (+SD) net plasma levels (ng/mL) over time when (1)NET alone was administered on Day 1 of Period 1 (circle markers), and(2) NET followed by 2 gram microgranule formulation of SYM-1219 wasadministered on Day 1 of Period 2 (triangle markers) (Group B1). FIG. 5illustrates the mean (+SD) net plasma levels (ng/mL) over time when (1)NET alone was administered on Day 1 of Period 1 (circle markers), and(2) 2 gram microgranule formulation of SYM-1219 was administered on Day1 of Period 2 and NET was administered on Day 2 of Period 2 (trianglemarkers) (Group B2). Table 4 below is a summary of the NET plasmapharmacokinetic parameters for Group B1 where (1) EE2/NET wasadministered on Day 1 of Period 1, and (2) EE2/NET was administeredfollowed by SYM-1219 on Day 1 of Period 2; and Group B2 where (1)EE2/NET were administered on Day 1 of Period 1, and (2) 2 g microgranuleformulation of SYM-1219 was administered followed by on Day 1 of Period2 and EE2/NET was administered on Day 2 of Period 2. Table 5 below is asummary of the percent of relative bioavailability for EE2 plasmapharmacokinetic parameters C_(max), AUC_(0-t), and AUC_(0-∞) for GroupB1 where (1) EE2/NET was administered on Day 1 of Period 1, and (2)EE2/NET followed by SYM-1219 2 grams were administered on Day 1 ofPeriod 2; and Group B2 where (1) EE2/NET was administered on Day 1 ofPeriod 1, and (2) 2 grams microgranule formulation of SYM-1219 wasadministered on Day 1 and EE2/NET was administered on Day 2 of Period 2.Table 6 is a summary of the percent of relative bioavailability for NETplasma pharmacokinetic parameters C_(max), AUC_(0-t), and AUC_(0-∞) forGroup B1 where (1) EE2/NET was administered on Day 1 of Period 1, and(2) EE2/NET followed by SYM-1219 2 grams were administered on Day 1 ofPeriod 2; and Group B2 where (1) EE2/NET was administered on Day 1 ofPeriod 1, and (2) 2 grams microgranule formulation of SYM-1219 wasadministered on Day 1 and EE2/NET was administered on Day 2 of Period 2.

TABLE 5 Summary of NET Plasma Pharmacokinetic Parameters by Period andTreatment - Pharmacokinetic Population (Part B) Group B1^(a) (N = 26)Group B2^(a) (N = 25) Parameter Period 1 Period 2 Period 1 Period 2C_(max) (ng/mL) n 26 26 25 25 Mean (SD) 9.18 (5.148) 10.07 (4.394)  9.63(5.419) 10.69 (5.169)  % CV   56.07   43.62   56.25   48.34 Median   8.00    9.45    8.16    9.39 Min, Max 2.7, 23.0 4.3, 20.7 3.6, 22.74.8, 28.6 T_(max) (h) n 26 26 25 25 Median    1.000    1.000    1.000   1.000 Min, Max 1.00, 4.00  0.50, 4.00  0.50, 2.08  0.25, 2.00 AUC_(0-t) (h*ng/mL) n 26 26 25 25 Mean (SD) 49.37 (34.588) 53.45(24.132) 61.35 (56.872) 61.16 (40.799) % CV   70.06   45.15   92.70  66.70 Median   38.67   48.94   41.66   44.53 Min, Max 16.7, 151.017.6, 117.6 17.4, 261.5 22.9, 185.9 AUC_(0-∞) (h*ng/mL) n 26 26 25 25Mean (SD) 57.79 (43.184) 62.39 (29.937) 74.98 (81.529) 71.53 (51.804) %CV   74.72   47.98   108.73   72.42 Median   45.33   54.33   47.35  51.59 Min, Max 18.0, 196.9 20.2, 144.5 20.3, 397.1 26.2, 224.6 t_(1/2)(h) n 26 26 25 25 Mean (SD) 9.60 (2.826) 9.60 (2.922) 10.04 (2.829) 9.51 (2.430) Median    8.71    9.12    9.29    9.19 Min, Max 6.2, 17.85.1, 16.4 6.8, 17.3 6.1, 16.6 λz (1/h) n 26 26 25 25 Mean (SD) 0.07709(0.018293) 0.07886 (0.023816) 0.07369 (0.017781) 0.07685 (0.016908)Median     0.07966     0.07642     0.07458     0.07539 Min, Max 0.0389,0.1125  0.0422, 0.1366  0.0401, 0.1022  0.0418, 0.1146  ^(a)Group B1 =EE2/NET on Day 1 of Period 1, then EE2/NET followed by SYM-1219 2 gramson Day 1 of Period 2. Group B2 = EE2/NET on Day 1 of Period 1, thenSYM-1219 2 grams on Day 1 and EE2/NET on Day 2 of Period 2. Source:Table 14.2.2.13; Listings 16.2.2.12.4-16.2.2.12.6

TABLE 6 Summary of the Percent of Relative Bioavailability for EE2Plasma Pharmacokinetic Parameters C_(max), AUC_(0-t), and AUC_(0-∞) byTreatment (Part B) % Ratio: Geometric 100*Test/Reference^(c) LeastSquares Geometric Parameter (LS) Means LSMean Treatment Period n Mean (%CV) (SE)^(b) % Ratio (SE)^(b) 90% C.I.^(b) C_(max) (pg/mL) Group B1^(a)Period 2 26 59.88 (42.19) 55.38 (2.728) 71.07 (4.951) (63.09, 80.05) Period 1 26 80.63 (26.84) 77.92 (3.839) Group B2^(a) Period 2 25 92.60(34.77) 87.16 (2.369) 104.96 (4.034) (98.28, 112.09) Period 1 25 89.12(36.36) 83.04 (2.257) AUC_(0-t) (h*pg/mL) Group B1^(a) Period 2 26615.55 (31.20) 590.74 (11.892) 94.26 (2.683) (89.78, 98.95)  Period 1 26643.67 (23.85) 626.75 (12.617) Group B2^(a) Period 2 25 668.63 (26.22)643.74 (10.529) 99.04 (2.291) (95.20, 103.04) Period 1 25 680.48 (28.91)649.96 (10.631) AUC_(0-∞) (h*pg/mL) Group B1^(a) Period 2 25 954.35(28.75) 924.75 (28.869) 105.37 (4.565) (97.84, 113.48) Period 1 26911.11 (29.39) 877.60 (26.363) Group B2^(a) Period 2 25 937.42 (33.60)882.24 (23.866) 93.32 (3.570) (87.41, 99.63)  Period 1 25 994.55 (28.91)945.39 (25.575) ^(a)Group B1 = EE2/NET on Day 1 of Period 1, thenEE2/NET followed by SYM-1219 2 grams on Day 1 of Period 2. Group B2 =EE2/NET on Day 1 of Period 1, then SYM-1219 2 grams on Day 1 and EE2/NETon Day 2 of Period 2. ^(b)From an ANOVA model for the log-transformedresults with effects treatment (Period 1: EE2/NET alone, Period 2:EE2/NET in combination with SYM-1219) and subject. ^(c)Test is Period 2[EE2/NET followed by SYM-1219 2 grams on Day 1 (Group B2) or SYM-1219 2grams on Day 1 and EE2/NET on Day 2 (Group B2)]; Reference is Period 1(EE2/NET Alone) Source: Table 14.2.2.15

TABLE 7 Summary of the Percent of Relative Bioavailability for NETPlasma Pharmacokinetic Parameters C_(max), AUC_(0-t), and AUC_(0-∞) byTreatment (Part B) % Ratio: 100*Test/Reference^(c) Geometric GeometricParameter LSMeans LSMean Treatment Period n Mean (% CV) (SE)^(b) % Ratio(SE)^(b) 90% C.I.^(b) C_(max) (ng/mL) Group B1^(a) Period 2 26 10.07(43.62) 9.16 (0.455) 113.18 (7.958) (100.37, 127.63) Period 1 26 9.18(56.07) 8.09 (0.402) Group B2^(a) Period 2 25 10.69 (48.34) 9.74 (0.483)116.46 (8.178) (103.27, 131.32) Period 1 25 9.63 (56.25) 8.36 (0.415)AUC_(0-t) (h*ng/mL) Group B1^(a) Period 2 26 53.45 (45.15) 48.72 (1.738)115.52 (5.828) (105.99, 125.92) Period 1 26 49.37 (70.06) 42.17 (1.504)Group B2^(a) Period 2 25 61.16 (66.70) 51.94 (1.361) 110.78 (4.104)(103.97, 118.03) Period 1 25 61.35 (92.70) 46.88 (1.228) AUC_(0-∞)(h*ng/mL) Group B1^(a) Period 2 26 62.39 (47.98) 56.42 (2.070) 116.27(6.032) (106.41, 127.04) Period 1 26 57.79 (74.72) 48.53 (1.780) GroupB2^(a) Period 2 25 71.53 (72.42) 59.95 (1.640) 108.75 (4.207) (101.78,116.19) Period 1 25 74.98 (108.73) 55.13 (1.508) ^(a)Group B1 = EE2/NETon Day 1 of Period 1, then EE2/NET followed by SYM-1219 2 grams on Day 1of Period 2. Group B2 = EE2/NET on Day 1 of Period 1, then SYM-1219 2grams on Day 1 and EE2/NET on Day 2 of Period 2. ^(b)From an ANOVA modelfor the log-transformed results with effects treatment (Period 1:EE2/NET alone, Period 2: EE2/NET in combination with SYM-1219) andsubject. ^(c)Test is Period 2 [EE2/NET followed by SYM-1219 2 grams onDay 1 (Group B2) or SYM-1219 2 grams on Day 1 and EE2/NET on Day 2(Group B2)]; Reference is Period 1 (EE2/NET Alone) Source: Table14.2.2.16

EE2 C_(max) was reduced by 29% (90% CI 63.09, 80.05) for Group B1; nochange in EE2 AUC was seen. EE2 PK was not altered for Group B2. NETC_(max) and AUC increased (13%) slightly for Group B1. NET C_(max)increased by 16% for Group B2; no change was seen for NET AUC. There wasno effect (90% CIs within 80-125%) on AUC_(0-t) or AUC_(0-∞) whenSYM-1219 was administered immediately after EE2/NET administration. WhenEE2/NET was administered 1 day after SYM-1219 administration, there wasno effect (90% CIs within 80-125%) from SYM-1219 on EE2 C_(max),AUC_(0-t) or AUC_(0-∞).

Simultaneous co-administration of EE2/NET and SYM-1219 appears todecrease the rate but not the extent of EE2 absorption. Administrationof EE2/NET one day after SYM-1219 appears to have no effect on EE2absorption.

NET C_(max), AUC_(0-t) or AUC_(0-∞) were increased by 13-16% and theupper value of 90% CIs were just above 125% when SYM-1219 wasadministered immediately after EE2/NET administration. When EE2/NET wasadministered 1 day after SYM-1219 administration the NET C_(max),AUC_(0-t) or AUC_(0-∞) were increased by 9-16%. The NET upper value ofthe 90% CI for C_(max) was 131% and there was no effect (90% CIs within80-125%) from SYM-1219 on AUC_(0-t) or AUC_(0-∞).

Simultaneous co-administration of EE2/NET and SYM-1219 may result insmall (13-16%) increases in the rate and the extent of NET absorption.Administration of EE2/NET one day after SYM-1219 may result in a small(16%) increase in the rate but not the extent of NET absorption.

SYM-1219 was safe and well-tolerated when taken alone or in combinationwith EE2/NET. The most common adverse events were headache and nausea.All adverse events were mild and resolved without sequelae. There wereno significant changes in vital signs, ECG or laboratory parameters.Concomitant administration of SYM-1219 with EE2/NET is not expected tohave an effect on contraceptive efficacy.

Conclusions: This study characterized the PK of EE2/NET with SYM-1219co-administration. Minor, clinically insignificant, reductions in EE2exposure were seen when SYM-1219 and EE2/NET were co-administered on thesame day. No change in EE2 exposure was seen when the SYM-1219 andEE2/NET doses were staggered by one day. No reductions in drug exposurewere evident for NET for either treatment group. These in vivo dataindicate that contraceptive efficacy for EE2/NET will not be altered bySYM-1219 administration. This was surprising in light of in vitrometabolism data indicating that concentrations of EE2 and NET may belowered and contraceptive efficacy may be adversely affected byco-administration of SYM-1219.

Example 3

This study was a Phase 2, multicenter, prospective, double-blind,placebo-controlled study to evaluate the effectiveness and safety ofSYM-1219 for the treatment of women with bacterial vaginosis. The studywas designed in accordance with FDA guidance for pivotal bacterialvaginosis trials with a primary end point clinical cure in the ModifiedIntent-to-Treat (mITT) population at day 21 to 30 versus placebo(two-sided test at alpha=0.05). Subjects were recruited to the studythey presented with the following Amsel criteria: presence of typicaldischarge. a positive KOH Whiff test vaginal fluid pH greater than orequal to 4.7, and the presence of “clue cells” (epithelial cells withadhering bacteria) on microscopic examination. Table 8 shows that a 2gram single-dose of SYM-1219 is effective for bacterial vaginosiscompared with placebo.

TABLE 8 Summary of Clinical Outcome Responder Rates by TreatmentModified Intent-to-Treat Population (mITT) SYM-1219 2 grams Placebo (N =62) (N = 62) n (%) n (%) Clinical Outcome Responder^(a) 42 (67.7) 11(17.7) Non-Responder 20 (32.3) 51 (82.3) P-value^(b) <0.001 95% ExactBinomial C.I. for Responder Rate 54.7, 79.1 9.2, 29.5 ^(a)ClinicalOutcome Responder is defined as a subject who had all three of thefollowing at TOC/EOS: normal vaginal discharge, negative KOH Whiff test,and clue cells <20%. ^(b)P-value versus placebo from CMH test adjustedfor BV strata (≤3 or >3 episodes in the past 12 months)

As can be seen in Table 9, a single dose of 2 grams of SYM-1219 wassurprisingly well tolerated.

TABLE 9 Summary of treatment-emergent adverse events by treatment safetypopulation SYM-1219 System Organ Class 2 grams Placebo Preferred Term (N= 72) (N = 72) Any Adverse Event Overall Subjects^(a), [n (%)] 14 (19.4)7 (9.7) Events, [n] 19  7 Infections and infestations OverallSubjects^(a), [n (%)] 5 (6.9) 6 (8.3) Events, [n] 7 6 Vulvovaginalmycotic Subjects^(a), [n (%)] 2 (2.8) 1 (1.4) infection Events, [n] 2 1Candida infection Subjects^(a), [n (%)] 0 0 Events, [n] 0 1 Chlamydialinfection Subjects^(a), [n (%) 1 (1.4) 0 Events, [n] 1 0 Fungalinfection Subjects^(a), [n (%) 0 1 (1.4) Events, [n] 0 1 GonorrhoeaSubjects^(a), [n (%)] 1 (1.4) 0 Events, [n] 1 0 Tooth abscessSubjects^(a), [n (%)] 1 (1.4) 1 (1.4) Events, [n] 1 1 Tooth infectionSubjects^(a), [n (%)] 1 (1.4) 0 Events, [n] 1 0 Urinary tract infectionSubjects^(a), [n (%)] 1 (1.4) 0 Events, [n] 1 0 Upper respiratory tractSubjects^(a), [n (%)] 0 2 (2.8) infection Events, [n] 0 2 Acutesinusitis Subjects^(a), [n (%)] 0 1 (1.4) Events, [n] 0 1 Nervous systemdisorders Overall Subjects^(a), [n (%)] 3 (4.2) 0 Events, [n] 3 0Headache Subjects^(a), [n (%)] 1 (1.4) 0 Events, [n] 1 0 DizzinessSubjects^(a), [n (%)] 1 (1.4) 0 Events, [n] 1 0 Dysgeusia Subjects^(a),[n (%)] 1 (1.4) 0 Events, [n] 1 0 Reproductive system and breastdisorders Overall Subjects^(a), [n (%)] 2 (2.8) 0 Events, [n] 3 0Vaginal discharge Subjects^(a), [n (%)] 1 (1.4) 0 Events, [n] 1 0Vaginal odor Subjects^(a), [n (%)] 1 (1.4) 0 Events, [n] 1 0Vulvovaginal pruritus Subjects^(a), [n (%)] 1 (1.4) 0 Events, [n] 1 0Investigations Overall Subjects^(a), [n (%)] 1 (1.4) 0 Events, [n] 2 0Alanine aminotransferase Subjects^(a), [n (%)] 1 (1.4) 0 increasedEvents, [n] 1 0 Aspartate Subjects^(a), [n (%)] 1 (1.4) 0aminotransferase increased Events, [n] 1 0 Renal and urinary disordersOverall Subjects^(a), [n (%)] 1 (1.4) 0 Events, [n] 1 0 ChromaturiaSubjects^(a), [n (%)] 1 (1.4) 0 Events, [n] 1 0 Gastrointestinaldisorders Overall Subjects^(a), [n (%)] 1 (1.4) 0 Events, [n] 1 0 NauseaSubjects^(a), [n (%)] 1 (1.4) 0 Events, [n] 1 0 Injury, poisoning andprocedural complications Overall Subjects^(a), [n (%) 1 (14) 0 Events,[n] 1 0 Thermal burn Subjects^(a), [n (%)] 1 (1.4) 0 Events, [n] 1 0Respiratory, thoracic and mediastinal disorders Overall Subjects^(a), [n(%)] 1 (1.4) 0 Events, [n] 1 0 Oropharyngeal pain Subjects^(a), [n (%)]1 (1.4) 0 Events, [n] 1 0 Surgical and medical procedures OverallSubjects^(a), [n (%)] 0 1 (1.4) Events, [n] 0 1 Tooth extractionSubjects^(a), [n (%)] 0 1 (1.4) Events, [n] 0 1 ^(a)Subjectsexperiencing multiple adverse events are only counted once within agiven cell.

TABLE 10 Summary of clinical outcome responder rates by bacterialvaginosis strata and treatment modified intent-to-treat population.SYM-1219 2 grams Placebo (N = 62) (N = 62) n (%) n (%) 3 or fewerepisodes in the past 12 months Clinical Outcome Responder^(a) 30 (73.2)10 (23.3) Non-Responder 11 (26.8) 33 (76.7) P-value^(b) <0.001 95% ExactBinomial C.I. for Responder Rate 57.1, 85.8 11.8, 38.6 4 or moreepisodes in the past 12 months Clinical Outcome Responder^(a) 12 (57.1)1 (5.3) Non-Responder  9 (42.9) 18 (94.7) P-value^(b) <0.001 95% ExactBinomial C.I. for Responder Rate 34.0, 78.2  0.1, 26.0 ^(a)ClinicalOutcome Responder is defined as a subject who had all three of thefollowing at TOC/EOS: normal vaginal discharge, negative KOH Whiff test,and clue cells <20%. ^(b)P-value versus placebo from CMH test Source:Listing 16.2.1.6

A 2 gram single dose of SYM-219 was found to be effective in treatingbacterial vaginosis in subjects having had 3 or fewer bacterialvaginosis infections/episodes in the past 12 months, as well as insubjects having had 4 or more bacterial vaginosis infections/episodes inthe past twelve months (See Table 10).

Example 3

In the mITT population, using a time stamped telephone diaryquestionnaire, on a five point scale composed of (1) Normal/Not anIssue, (2) Mildly Abnormal, (3) Moderately Abnormal, (4) SeverelyAbnormal and (5) Very Severely Abnormal, the proportion of women on a 2g dose reporting 3-5 for vaginal discharge declined from 59% on day 1,to 30% on day 3 (˜48 hours), and to 14% on day 7 as can be seen in Table11. The proportion of women on a 2 g dose reporting 4-5 for vaginaldischarge declined from 36% on day 1, to 11% on day 3 (˜48 hours), andto 0% on day 7 as can be seen in Table 11. The proportion of women on a2 g dose reporting 3-5 for vaginal odor declined from 66% on day 1, to20% on day 3 (˜48 hours), and to 9% on day 7 as can be seen in Table 11.The proportion of women on a 2 g dose reporting 4-5 for vaginal odordeclined from 38% on day 1, to 9% on day 3 (˜48 hours), and to 0% on day7 as can be seen in Table 11

TABLE 11 Results of Telephone Diary Questionnaire Day mITT Points 1 2 34 5 6 7 EOS 2 g - 1 6 10% 9 17% 13 24% 19 35% 21 43% 22 47% 24 55% 3668% Discharge 2 18 31% 20 38% 25 46% 22 40% 17 35% 15 32% 14 32% 9 17% 313 22% 15 29% 10 19% 8 15% 4  8% 7 15% 6 14% 4  8% 4 17 29% 3  6% 3  6%5  9% 6 12% 2  4% 0  0% 3  6% 5 4  7% 5 10% 3  6% 1  2% 1  2% 1  2% 0 0% 1  2% Total 58 52 54 55 49 47 44 53 2 g - 1 8 14% 10 19% 20 37% 2749% 28 58% 29 62% 33 75% 36 69% Odor 2 12 21% 23 44% 23 43% 18 33% 1225% 12 26% 7 16% 7 13% 3 16 28% 10 19% 6 11% 6 11% 5 10% 5 11% 4  9% 917% 4 17 29% 8 15% 4  7% 4  7% 3  6% 1  2% 0  0% 0  0% 5 5  9% 1  2% 1 2% 0  0% 0  0% 0  0% 0  0% 0  0% Total 58 52 54 55 48 47 44 52

While the illustrative embodiments of the invention have been describedwith particularity, it will be understood that various othermodifications will be apparent to and can be readily made by thoseskilled in the art without departing from the spirit and scope of theinvention. Accordingly, it is not intended that the scope of theembodiments above be limited to the examples and descriptions set forthhereinabove but rather that the invention be construed as encompassingall the features of patentable novelty which reside in embodimentsdescribed herein, including all features which would be treated asequivalents thereof by those skilled in the relevant art.

1.-52. (canceled)
 53. A method of treating trichomoniasis in a subjectin need thereof comprising administering to the subject atherapeutically effective amount of secnidazole in a microgranuleformulation, wherein the microgranule formulation comprises a pluralityof microgranules, and wherein secnidazole is the sole drug in themicrogranule formulation.
 54. The method of claim 53, wherein theplurality of microgranules having a particle size in the range of 400micrometers to 841 micrometers.
 55. The method of claim 53, wherein thetherapeutically effective amount of secnidazole is an amount ofsecnidazole that exhibits a maximum plasma concentration (C_(max)) ofabout 17.4 μg/ml to about 26.5 μg/ml in the subject.
 56. The method ofclaim 53, wherein the therapeutically effective amount of secnidazole isan amount of secnidazole that exhibits a C_(max) of about 34.5 μg/ml toabout 58.3 μg/ml in the subject.
 57. The method of claim 53, wherein thetherapeutically effective amount of secnidazole is an amount ofsecnidazole that exhibits a time to maximum plasma concentration(T_(max)) of about 2 hours to about 6 hours in the subject.
 58. Themethod of claim 53, wherein the therapeutically effective amount ofsecnidazole is an amount of secnidazole that exhibits a T_(max) of about3 hours to about 4 hours in the subject.
 59. The method of claim 53,wherein the therapeutically effective amount of secnidazole is 2 grams.60. The method of claim 53, wherein the therapeutically effective amountof secnidazole in the microgranule formulation is administered orally.61. The method of claim 53, wherein the microgranule formulation furthercomprises sugar spheres, povidone, polyethylene glycol, ethyl acrylatemethyl methylacrylate copolymer, talc, or a combination thereof.
 62. Themethod of claim 53, wherein the microgranule formulation is administeredto the subject by integrating it into a food substance.
 63. The methodof claim 62, wherein the food substance is applesauce, yogurt, orpudding.
 64. The method of claim 62, wherein integrating is mixing themicrogranule formulation into the food substance.
 65. The method ofclaim 53, wherein the subject is a female.
 66. The method of claim 53,wherein the subject is a pregnant female
 67. The method of claim 53,wherein the subject is suffering from bacterial vaginosis.
 68. Themethod of claim 53, wherein the therapeutically effective amount ofsecnidazole in the microgranule formulation is administered as a singledose.
 69. The method of claim 53, wherein the therapeutically effectiveamount of secnidazole in the microgranule formulation is administeredwith an additional compound selected from ethinyl estradiol (EE2),norethindrone (NET), or a combination thereof.
 70. The method of claim69, wherein the additional compound is administered on the same day asthe therapeutically effective amount of secnidazole in the microgranuleformulation.
 71. The method of claim 69, wherein the additional compoundis administered on a different day as the therapeutically effectiveamount of secnidazole in the microgranule formulation.
 72. The method ofclaim 53, wherein the microgranule formulation does not affect thecontraceptive efficacy of an additional compound selected from EE2, NET,or a combination thereof.
 73. A method of treating trichomoniasis in asubject in need thereof comprising administering to the subject atherapeutically effective amount of secnidazole in a microgranuleformulation, wherein the microgranule formulation comprises a pluralityof microgranules, each microgranule having a particle size in the rangeof 400 micrometers to 841 micrometers, and wherein secnidazole is thesole drug in the microgranule formulation.
 74. The method of claim 73,wherein the subject is suffering from bacterial vaginosis.